***Historical introduction

What is the tissue that secretes cerebrospinal fluid in the ventricles?

choroid plexus

In explaining fluorescence, why is the emission a longer wavelength than the excitation?

energy is lost before a hoton is re-emitted

In the knee-jerk reflex, answer either (1) Where is the cell body of the motor neuron? or (2) Where is the cell body of the sensory neuron?

ventral horn in gray matter of spinal cord, in dorsal root ganglion PNS

"Your patient is having a stroke. Quick! Give him some TPA." Under what circumstances would tissue plasminogen activator be contraindicated?

hemorrhagic stroke

Confocal microscope. Answer either (1) How did they make tau look red and tubulin look green in that textbook micrograph? or (2) What property of the technology allowed Dr Stark's student make a Quicktime movie focusing through the depth of the Drosophila retina?

bind green- or red-emitting fluorophores to secondary antibody that binds primary antibody to tau and tubulin, optical sectioning = low depth of focus

"Histochemical fluorescence." What substance was seen in the fluorescence microscope when the tract from the substantia nigra to the striatum (basal ganglia) was visualized?

dopamine combined with formaldehyde

"Fluorescent- or gold-labeled secondary body." Answer either (1) What specific molecule does it bind to? or (2) Why gold? (referring to immunocytochemistry)

primary antibody, electron dense

A specialized brain scan technique shows a defect in a pathway in blind subjects. What lobe does this tract go to?

occipital

The cells that make axons that project from the eye to the brain are called ganglion cells. WHY is this nomenclature not correct?

"ganglion" is a term applied to the peripheral nervous system. the retina is considered to be central nervous system

The caudate, putamen and globus pallidus receive input that is deficient in Parkinson's disease. What is the overall function of this system.

smoothening out motor movements

In the knee-jerk reflex, the flexor is inhibited. How?

through an inhibitory interneuron in the gray matter of the spinal cord

How was Ramon y Cajal able to produce pictures of neurons in intricate detail?

Golgi's technique fully stained one cell. Since surrounding cells were not stained, he could draw the ones that were stained

"Histochemical fluorescence was used in the 1960's to trace the dopamine tracts from the substantia nigra." Answer either (1) What was it that fluoresced? Or (2) How did they (researchers in the 1060's) determine these tract pathways?

(1) dopamine (reacted chemically) (2) histological sections allowed following the tracks that fluoresced

"A secondary antibody, a goat anti-mouse IgG, is attached to a fluorescent label like fluorescein." Answer either (1) What kind of a microscope would you use? Or (2) What kind of molecule would the primary antibody attach to? Or (3) Where is this molecule that the primary antibody attaches to?

(1) fluorescence or confocal microscope (2) the protein you wanted to stain (3) on a microscope slide with a slice of the tissue being studied

What makes it so that Tau, a microtubule-binding protein, fluoresces red in the confocal microscope?

need to bind antibodies tagged with fluorescent dye

What function is localized to Brodmann area 17 in the occipital lobe?

vision

Why was the technique developed by Golgi and utilized by Ramon y Cajal so useful for studies of cellular architecture?

by staining very few cells (in their entirety) they could be seen even though many other cells were nearby

For the knee jerk reflex, where (be specific) is the cell body of the motor neuron?

ventral horn of gray matter in spinal cord

One of the most famous examples of localization of function is Broca's area, used for what?

language

Why would tissue plasminogen activator (TPA) be contraindicated in 20% of stroke victims?

do not want to interfere with clotting if there is hemorrhage

A coronal section of the brain was shown revealing the caudate, putamen and globus pallidus, involved in coordinating motor movements. These structures are collectively referred to as what?

basal ganglia

Why is the optic "nerve" (the second cranial "nerve") actually a tract?

eye and this "nerve" are part of the CNS

What information (and in what direction) is carried by axons of the cells in the dorsal root ganglion?

somatosensory (also muscle stretch, etc.) afferent

Why might half of your brain be saved it there were a unilateral occlusion affecting one internal carotid artery?

because the circle of Willis would bring blood from the other side

What is the huge decussation seen as white matter in a midsagittal section of the brain?

corpus callosum

If Santiago Ramon y Cajal (famous proponent of cell theory) knew what we knew now, how would he have used the chemical synapse in his arguments against Camillo Golgi's reticular theory?

Cells, being separate, must communicate

What is the function of Brodmann's area #4, the precentral gyrus?

Motor cortex

The text figures with several proteins (like tau plus tubulin) labeled different colors in a nerve cell look really nice! One reason is that out-of-focus cells do not degrade the image. How did "they" acheive this?

Confocal microscope (optical sectioning, low depth of field)

The "nigro-striatal dopamine tract" is implicated in Parkinson's disease. It goes to the striatum. Where does it come from?

substantia nigra

Under what circumstances would you label your antibody with colloidal gold vs a fluorescent dye?

coloidal gold for electron microscopy, fluorescent dye for standard and confocal fluorescence microscopes

What is the function of the choroid plexus situated in the ventricles?

secrete cerebro spinal fluid (CSF)

Why are the "basal ganglia" called "basal nuclei" in some treatments (like the transparency from the introductory book that I showed)?

cells and connections in the CNS are called nuclei

What substance is missing in gray matter (but is present in white matter and makes white matter white)?

myelin

What colossal body is seen in mid-sagittal section that connects left and right hemispheres?

corpus callosum

What is the anatomical name of the combined medulla, pons and midbrain?

brain stem

For which kinds of stroke might you use desmoteplase (from vampire saliva)?

those caused by thrombus or embolism

How could all the details of the dendritic tree of a cerebellar Purkinje cell be revealed when that cell is in the neighborhood of "zillions" of other cells?

Golgi staining technique only highlights one cell out of how many

What optical phenomenon, important in microscopy, was demonstrated when I shined an untraviolet (UV) light (that you could not see) onto my shoe laces and they shined a bright blue?

fluorescence

Suppose I'm interested in the subcellular localization of a protein (such as tau, actin, tubulin or rhodopsin). Why do I need two antibodies to visualize the protein?

one to bind the protein of interest, the secondary directed against the first with fluorescent or electron dense label

Scientists in Brocca's time needed to wait until autopsy to find the localization of function damaged by stroke (or tumor or whatever). What allows us to see into the brain of a subject or patient nowadays?

imaging (CT, PET, MRI)

Low depth of field and optical sectioning allow unique computer-generated views in which a stack of optical sections can be rotated. What technique is this?

Confocal microscopy

Answer at least one of these two: This particular fluid filled chamber is hard to see because it is thin and cut right down the middle when we make (name of?) this particular type of cut, right down the middle brain.

third ventrical, midsaggital

The left side of the brain controls the right side of the body because the tract (what is the official word for when the tract crosses from one side to the other?).

decussates

What apparatus or type of surgery do you need to put a lesion deep into a live rat's brain?

stereotactic (same word for both questions)

What's the name of the most famous type of neurological surgery (psychosurgery for psychiatric patients) chopping off connections to one part of the brain?

frontal lobotomy

Why would a neuroscience snob tell you that the cell bodies that make the optic nerve should not be called "ganglion cells?"

because they are part of the central nervous system (hence nuclear) would be the more accurate term

I showed you two coronal sections. One showed caudate and putamen. The other showed the third of the three basal ganglia called (what?).

globus pallidus

Answer at least one of these: Cell bodies right outside the dorsal root of the spinal cord carry (what type of?) information in what direction (official word of toward the central nervous system)?

somatosensory, afferent

I showed you a spectacular cell, the cerebellar Purkinje cell. How could Santiago Ramon y Cajal create that picture? Answer either (1) How did he do that way back around "the turn of the century (around 1900)? or (2) How could he see that one cell when there were "zillions" of other neurons near it?

he drew it carefully, Golgi's staining technique highlights single cells in their entirety

Answer one of these two RELATED questions about the merits of confocal microscopy (in comparison with standard fluorescence microscopy). (1) Why do the pictures I showed you from the text look so clear? Or (2) How come I was able to put together a stack of images to rotate or to focus through?

"optical sectioning," everything out of the plane of section is not collected and many sections can be put together in a stack

A fancy brain imaging technique was used by former neuro student Epstein to show that early blind subjects has less tract connecting the thalamus to the (answer either) (1) Brodman area #? Or (2) lobe?

#17, occipital

Medulla plus pons plus midbrain is called (what?).
 
brainstem
 
How could somebody in the mid 1800's identify a specific area in the cerebral cortex as being critical for language and speech?
 
See the brain of a speech challenged patient upon autopsy
 
Occlusion of one internal carotid might not be fatal because of (what structural adaptation?).
 
circle of Willis
 
In a mid-sagittal brain section, the most conspicuous tract seen connects one side (hemisphere) of the brain with the other. What is that called? 
 
Corpus callosum

Why was Ramon y Cajal's body of work using Golgi's technique a contribution worthy of the Nobel Prize?
 
He showed the complete anatomy of neurons in many systems and developed cell  theory
 
Lashley, concluding that memories were stored all over the cerebral cortex, came up with the term "equipotentiality." By contrast, textbooks colorize the cortex to present what alternative viewpoint on how the cortex represents specific sensory and motor systems?
 
Localization of function
 
Gray matter areas in the brain with cell bodies and synaptic connections (such as the so-called "basal ganglia") are supposed to be called (what?).
 
nuclei
 
For the knee-jerk reflex, cells that connect (what?) to the spinal cord are found in the dorsal root ganglion.
 
Muscle spindle, stretch receptor
 
Why are there cervical and lumbar enlargements in the spinal cord?
 
More spinal motor neurons for the forelimbs and hindlimbs
 
In the 1960's, scientists determined that the substantia nigra sends dopamine all over the brain. How did they do this?
 
Histochemical fluorescence
 
You buy some antibody linked to 10 nm colloidal gold from a company. To localize aardvarkia, the protein you are studying in the aardvark caudate, answer either (1) What other reagent do you need to make or buy? Or (2) What apparatus will you use to visualize the colloidal gold and the aardvarkia protein it labels?
 
Primary antibody against aardvarkia, transmission electron microscope
 
Where do you expect to find spines, those structures with tubulin and actin, in the nervous system?
 
Where the postsunaptic area is, cell body or dendrite
 
"Postsynaptic density" - what technique and "staining" affords us the resolution to see this as a "density?"
 
need to stain for transmission electron microscopy with heave metals

***Neurons and Glia


***Bioelectric

An action potential is (1) all-or-none, (2) non-decremental, and (3) in the direction of making the inside of the cell more positive. Pick one of those three attributes and say how a synaptic potential differs if it differs.

potentials can add to each other, they get smaller with distance, they may also be hyperpolarizing

"Cole and Curtis's bridge went out of balance." What did we learn from their 1939 work on the squid giant axon with the Wheatstone bridge?

conductance goes up as the action potential passes

"A square wave of current injection led to a hyperpolarization that was low pass filtered." That different shape was because of what property of the membrane?

capacitance

In the Goldman equation, concentrations (in and out) of sodium, potassium and chloride, and permeabilities for all three ions, are shown. There is an equivalent circuit (with electrical components) for the Goldman equation. What is used in the circuit model for the sodium permeability? Be thorough enough in your answer to address what happens to sodium permeability during the action potential.

a variable resistor (potentiometer) that lets sodium permeability go up

Current flows through (what?) in the patch clamp technique that earned Neher and Sackman the 1991 Nobel Prize.

individual channels

Ouabain is applied to the cell. Answer either (1) Why does the membrane potential change by a few mV? or (2) Why doesn't the membrane potential go away right away?

3 sodiums to 2 potassiums make the pump electrogenic, otherwise potentials are based on huge reservoirs of ion gradients that would run down very slowly if the pump were blocked

In Hodgkin and Keyne's1955 experiment, what happened to the efflux of radioactive sodium mediated by the "sodium pump" when extracellular potassium, already low, was really lowered?

it decreased sharply because sodium transport relies on exchange with potassium transport

"Inside a Ca2+-sequestering cistern inside a cell is sort of like outside the cell." For these two compartments (inside, say, sarcoplasmic reticulum and extracellular fluid), how does the Ca2+ concentration relate to the cytoplasmic calcium ion concentration?

calcium outside the cell is higher than in cytoplasm

In an experimental validation of the theory, it was shown that the slope equals 58 mV per 10-fold change in K+ gradient. After the researchers had an electrode measuring the resting potential, what did they do?

change the extracellular potassium ion concentration

Variable resistors are in an equivalent circuit model of the Goldman equation. Which resistor is changed, and in what direction, at the start of the action potential?

the sodium resistance is decreased

When an invertebrate needs a fast action potential, it has a giant axon because it lacks (what specialization that vertebrates posess to speed the action potential?).

myelin

A micropipette is touched to the membrane but not inserted into the cell. Answer either (1) What is this technique called? Or (2) What would it allow you to do?

(1) patch clamp (2) record current from individual channels

When a square wave of current is injected into the cell, the Voltage change is gradual because of (what property of the membrane?).

capacitance

Cole and Curtis showed that a bridge went out of balance in the squid giant axon as the action potential went on by. What fundamental conclusion did they draw from this?

resistance went down (conductance up)

"Theoretically, sodium should not flow in when the sodium channels open." Answer either (1) Whose theory? Or (2) Why not?

(1) Nernst (2) chemical and electrical gradients equal and opposite

"If I could wave a magic wand and instantly abolish the sodium potassium pump while I had an electrode in the cell," Answer either (1) Why would the membrane potential NOT change a lot (immediately)? Or (2) Why WOULD the membrane potential change immediately by just a few mV?

(1) gradients were established and would not run down quickly (2) the electrogenic sodium pump is based on the imbalance (3 sodium ions in to 3 potassium ions out)

Hodgkin and Keynes found that removing extracellular K+ decreased the Na+ efflux from the "sodium pump." Why would this be the case?

even though extracellular potassiun is low, the Na+-K+ATP needs to pump K+ to pump Na+

Paving the way for the Nobel Prize winning Hodgkin and Huxley work, what could you conclude from the Cole and Curtis finding that the AC bridge went out of balance as the
action potential goes by?

conductance increased

The time constant (=RC) describes the properties of what kind of filter placed before the input of a differential amplifier?

low (or high) pass (or cut-off)

Faraday's constant is the charge of a mole of ions, 9.65 x 104 coulombs/mole = Avagadro's number x the elementary charge (charge of a single ion). What would be the units of
the elementary charge?

coulombs per ion

An appropriately low dose of the cardiac glycoside digitalis would improve myocardial contractility by blocking what?

sodium pump directly, sodium calcium exchange indirectly

The equilibrium assumption in the derivation of the Nernst equation means that what two gradients are equal and opposite?

electrical and chemical

Why is the "sodium pump" electrogenic?

because of the imbalance (2K+/3Na+)

If I were on the ordinate (Y axis) and V were on tha abscissa (X axis), what electrical term is used to describe the slope of the line?

conductance (g)

How do you use the patch clamp method to determine the properties of a channel gated by intracellular ligands like cAMP or cGMP?

get the channel, break off that hunk of membrane, then you can dip the inside of the channel

In the numerator of the Goldman equation, we find intracellular potassium and sodium but extracellular chloride. Why the difference?

Cl is -, others are +

On an oscilloscope (polygraph or computer), an action potential is a graph of what as a function of what?

voltage, time

In the circuit diagram model for the Goldman equation, potentiometers are used instead of resistors. Why?

resistance is variable

Why does a glass micropipette have high resistance?

it is so small, a narrow path of electrolyte

In contrast with "all-or-none" give the general term for those smaller potentials of variable size that can be either depolarizing or hyperpolarizing. (One is for sensory receptor potentials the other for synaptic potentials.)

generator-sensory, graded-synaptic

Describe the technique developed by the Nobel Prize winners Neher and Sackmann that allowed the measurement of currents through single channels.

patch clamp puts the tip of an electrode up against a channel

The action potential is all-or-none in part because you cannot trigger one spike on top of another. In other words, there is a refractory period. What property of the sodium channel is responsible?

inactivation

What molecule has an ouabain binding site?

the Na+-K+-ATPase (sodium pump)

I said, "capacitance adds delays." Draw the graphs for a square wave of current injection and the corresponding hyperpolarization to show the low pass filtering of membrane capacitance.

look on p 61

What imbalance makes ATPase electrogenic?

3 Na+/ 2 K+

Faraday's constant, the charge of a mole of ions in Coulombs per mole, is used to solve for which specific component of energy in the derivation of the Nernst equation?

electrical component

Why didn't the efflux of radioactive Na+ go to zero immediately when Hodgkin and Keynes blocked ATP synthesis with DNP (dinitrophenol)?

the pump keeps working until the ATP runs out

What factors are applied to the concentrations of Na+ and K+ to allow the Goldman equation to account for both resting and action potentials?

relative permeabilities (conductances)

After being open, sodium channels have something, and the word "close" does not fully convey the meaning of (what is the correct word)?

inactivate

"Other than channels and pumps, membranes do not pass ions well." Why not?

The center of the membrane is hydrophobic

In contrast with the term "all-or-none," what does the term "graded" signify in describing membrane potentials?

They can be of varying size

n a 1902 paper, Bernstein, applying the principles learned from Nernst, proposed that K+ permeability was lost during the action potential. In what way was this wrong? In what way was it insightful?

Wrong, K+ permeability was not lost, right - relative K+ permeability less because that of Na+ is more

After assuming that the energies of two compartments are equal, algebra boils the Nernst equation down to saying that the membrane voltage is equal and opposite to what?

chemical gradient

I told a story about how capacitors hold a charge (that can shock a person when they discharge). How did that story relate to the passive voltage response of the membrane at the end of stimulation of the membrane by a square wave of current?

After stimulation ends abruptly, membrane voltage returns to baseline gradually

Right when ATP converts to ADP to power the sodium pump, what becomes of the inorganic phosphate?

Before it is free, it is bound to pump molecule

Pick either word, "cardiac" or "glycoside" and tell me why the expression applies to digitalis.

In heart muscle cells, blocks Na+ pump slows Ca2+/Na+ exchanger, increasing intracellular Ca2+ for stronger contractility, glycoside bonds.

In Hodgkin and Keynes' classic experiment on the sodium pump, how did they obtain numbers for the Y-axis (ordinate) that relate to sodium efflux?

measured radioactivity aftyer loading axon with radioactive sodium

Why is there a direct (electrogenic), though small, contribution of the Na+-K+-ATPase to the membrane potential?

because 3 Na+'s are pumped per 2 K+'s

"Slope = 58 mV per tenfold change in K+ gradient." Answer either of the following: How did they do this experiment? OR Why would it be expected to be this way?

Change extracellular potassium, cause voltage = -58 times the log (to the base 10) of the ion gradient

What does the Goldman equation tell us beyond the Nernst equation?

takes into account pooled voltage based on sodium, potassium and chloride (ion gradients and relative permeabilities)

When the AC (fast) Wheatstome bridge of Cole and Curtis swung out of balance, what did that tell us about the membrane events at that moment?

resistance changed (decreased) during action potential

"The cause of the resting potential is potassium ions flowing through the potassium channel." Why is this not the whole truth?

in the equilibrium assumption, no ions need to flow for voltage

Why would an inside out patch be useful in studying channels gated by ligands generated by the intracellular signal transduction cascade?

can "dip" it into solutions with such ligands (like cAMP and cGMP

Address 1, 2, or 3. Ouabain is a (1) cardiac (2) glycoside that binds (3) a very important molecule.

can strengthen a weak heart beat, that describes the chemical bond, the sodium pump

Hodgkin and Keynes were studying the properties of (what?) when they measured the efflux of radioactive sodium from the squid giant axon.

the sodium pump

Why might a glass micropipette distort the shape of an action potential without the proper amplifier?

has high resistance and capacitance, hence makes a low pass filther that clips a fast signal

Membranes (and glass micropipettes) have resistance. But they also have (what else?) that causes the voltage change to be delayed.
 
capacitance
 
Permeability of a particular ion, say sodium, across the membrane is inversely related to the resistance across the membrane for that ion and directly related to (what electrical property?).
 
conductance
 
Explain why the electrical potential calculated with the Nernst equation is called the equilibrium potential.
 
The assumption is tantamount to equilibrium (electrical and chemical potentials equal and opposite
 
Answer one of these about Cole and Curtis's AC Wheatstone bridge (1) What is meant by "voltage divider?" or (2) What did they conclude on the basis of their bridge going out of balance?
 
Two resistors in a row where the voltage acroee each is IR, resistance decreases (during the action potential
 
Describe or draw how Nobel prize winners Neher and Sackmann measured current through individual channels.
 
The patch clamp electrode nudges against the membrane where there is one channel
 
Why did the efflux of radioactive sodium from the squid giant axon eventually decrease when DNP inactivated the mitochondria in Hodgkin and Keynes classic experiment in the 1950s?
 
without ATP, the sodium pump stops
 
You are recording the membrane potential (resting potential). What happens to this potential if you replace the extracellular fluid with potassium chloride at the same concentration as the intracellular concentration?
 
It goes to zero (from, say, -70)


***Action Potentials

Discussing passive spread of a decremental potential, the current spreading down the axoplasm gets smaller with distance from a place where a stimulus is applied. What happened to the current that was no longer going down the axoplasm?

it leaked through the axon membrane's resistance and capacitance

What does the space constant and the time constant have to do with why squids have giant axons?

cable equation's space constant varies with the square root of the radius while the time constant is independent of the radius, and the space constant over the time constant of passive spread ought to predict the action potential speed

Loss of what hormone, from an adrenalectomy, would make a rat crave salt?

aldosterone

The lecture and figures refer to a sodium channel that is about to be depolarized to threshold by an upstream action potential as "closed." Right after the action potential has passed, what term do we use to describe the status of the sodium channel?

inactivated

Why would long QT syndrome limit a person's ability to respond to stress?

inability to have shorter action potential in the ventricualr myocardium would limit how fast the pulse can get

Why, when the voltage of the squid giant axon is clamped at +65 mV (inside positive), does the early current flow out instead of in?

despite the fact that sodium is going up against its ion gradient, the driving potential, the voltage minus the sodium equilibrium potential, would drive current that direction

A family of "I-T curves" were used by Hodgkin and Huxley to generate two "I-V curves." Say something about these curves.

the "family" was for different voltage clamp levels, giving the V on tie I-V curves. early and late times were chosen tor the two I-V curves. the early curve showed the negative conductance region representing the soduim channel activation

"The space clamp meant that voltage clamping was done along the whole axon." Why would this be more useful than firing a real action potential?

realistic (measurable, not infinitessimal) currentscould be measured

How much current should be carried by sodium at the sodium equilibrium potential?

none

What are the differences in how four components form a channel for Shaker vs. Electrophorus?

4 proteins for shaker, 4 domains of one protein in electrophorus

At one time they thought that the positively charged amino acids in S4 lined the channel, but eventually they agreed that S4 did (what?)?

sensed toe voltage for gating to cause a conformational change for activation

Aldosterone sensitive neurons mediate an animal's specific appetite for what important substance relevant to action potentials?

sodium

"The time constant is independent of radius." Then why are giant axons faster?

the space constant relates to the square root of the radius

Current goes down the axoplasm from the location where the action potential is located. The amount of current gets smaller as a function of distance from the action potential. Why does it get smaller?

it leaks out through membrane resistance and capacitance

In a Voltage clamp experiment, on the I-t curve, there is an early inward current unless the voltage is clamped (at about what level?).

the sodium eauillibrium potential (+55 mV)

Why was it useful to obtain conditional mutants (like temperature- or ether-sensitive mutants), rather than ordinary mutants, to isolate genes like shaker and ether-a-go-go in Drosophila?

channelopathy mutants would be lethal

Why would long QT syndrome interfere with the body's response to stress?

can't get the heart beats short enough to speed up the heart rate

What part (domain) of the Shaker protein is responsible for inactivation?

a stopper (ball of amino acids) at the N-terminal end

Although it is thick mucus in the lungs that is life-threatening in cystic fibrosis victims, it is a channel that is deficient. What kind of channel?

a chloride channel

What causes the S4 transmembrane span of the sodium channel to rotate?

detection of the depolarizing voltage

Why was Electrophorus electricus useful in channel research?

sodium chasnnels were so plentiful in the electric organ that they could be isolated and characterized

Parathormone, calcitonin, and (what other hormone?) help to maintain appropriate levels of blood Ca2+?

vitamin D

How did the electric eel Electrophorus electricus assist in the isolation of a channel?

sufficient concentration of sodium channel to allow characterization

In theory, and in data, what is the direction and amount of Na+ current when the voltage in the axon is clamped to the Na+ equilibrium potential?

none

Paving the way for the Nobel Prize winning Hodgkin and Huxley work, what could you conclude from the Cole and Curtis finding that the AC bridge went out of balance as the
action potential goes by?

conductance increased

In terms of amino acid sequence, how does the S4 of the voltage-gated Na+ channel differ from the typical transmembrane alpha helix?

charged arginines or lysines every 3 or 4 amino acids

To hold the voltage of a squid giant axon at a clamped level of 0 mV, Hodgkin and Huxley had to pump current out through the membrane at 0.5 ms (fairly early) to compensate for
what?

sodium current

What does tetrodotoxin block?

the sodium channel

"Long QT syndrome can be caused by a mutation of HERG." Translate.

genetic long myocardial action potential

How does the space constant of an axon relate to the axon's size?

with square root of radius

Some potassium channels do show inactivation. What part of the molecule is responsible?

stopper on the N-erminus

CSNB is a channelopathy. S=stationary (not progressive degeneration). NB=night blindness (affecting rod photoreceptors). Why is the term C=congenital applied?

it's genetic

An action potential depolarizes the axon ahead of it to threshold, and that is why the action potential propagates. It would also depolarize the axon behind it. Why does it not cause a
backward action potential?

refractory potential, inactivation

Selecting for conditional channel mutants, like temperature sensitive mutants, has been especially useful in Drosophila. Why not just isolate regular mutants?

they might be lethal

Why would two resistors in series connected to a battery be called a Voltage divider?

Two sources of voltage (Ohm's law) E=IR, E = IR1 + IR2, used in Wheatstone bridge

In discussing the passive properties (i.e. without an action potential), the current gets smaller with distance from the stimulus going along the axoplasm (down the inside of the axon). Why does it get smaller?

along the way, it is lost through the membrane (the membrane's resistance and capacitance)

The Shaker K+ channel is a tetramer of proteins that each cross the membrane 6 times. Why is the Electrophorus Na+ channel called a pseudotetramer instead?

because one huge molecule has 4 repeated domains each the size of one shaker channel protein

When (or why) is there a negative conductance region in the I-V curve in Voltage-clamp data?

early, when Na+ channels activate then inactivate

What would be the cause of death if you ate a puffer fish?

Na+ channel block, no action potentials

What does an alpha helix, namely S4, with positively charged (basic) amino acids [arginine (R) or lysine (K)] every 3 or 4 amino acids do for the action potential's sodium channel?

it detects Voltage to gate the activation of the channel

Cole and Curtis already knew that the conductance went up as the action potential went by. Hodgkin and Huxley went a bit further. Which conductance(s) went up?

Na+ and K+

Give the name of at least one "channelopathy" (genetic disease resulting from a mutation affecting a channel protein).

paralysis, myotonia, long QT syndrome, congenital stationary night blindness

You remove both adrenal glands of a rat and let it recover. Answer either (1) What is different about the animal's specific appetite? Or (2) This is explained by the absence of what hormone?
 
Craves salt (NaCl) b/c of loss of aldosterone
 
A certain voltage is applied at one place in an axon. On the basis of passive spread only (no action potentials) what would be the voltage (relative to the applied voltage) one space constant away? (Your answer can be very approximate.)
 
1/3 approximates 1/e
 
The voltage of an axon is clamped from the resting potential to 0 mV. At 0.7 ms (early), Answer either (1) What direction is the current? Or (2) How is this current changed if 460 mM sodium chloride is replaced by choline chloride?
 
In, there is no sodium current if there is no sodium
 
In terms of the protein, what would be the genetic explanation of permissive vs restrictive temperatures in a temperature sensitive conditional mutation?
 
A missense mutation might only disrupt function if temperature denatures the protein
 
For long Q-T syndrome, answer either (1) What cell type has a long action potential that should become shorter in strenuous exercise but does not? Or (2) The channel was first found because what conditional behavior was first noticed in Drosophila mutants?
 
Ventricular myocardial cell, shaking under ether anesthesia
 
Why do they distinguish Shaker vs Electrophorus channels as tetramer vs pseudotetramer?
 
It takes 4 shaker proteins, the electrophorus protein has all 4 domains in one big molecule
 
It seems like there ought to b e salt sensitive neurons to explain sodium appetite. However, former neuro class student Joel Geerling showed thqat neurons were sensitive to a hormone. What hormone?

aldosterone

In passive propagation (cable properties of the axon) why does the current carried down the axoplasm get smaller as you go further from the applied voltage?

leaks out through the membrane

In the classic Hodgkin-Huxley voltage clamp experiments, How did they show that the early inward current was carried by sodium ions?

replace extracellular fluie with sodium free solution

Explain absolute refractory period on the basis of a property of a channel.

an inactivated channel cannot be activated (but a closed channel can)

What would be a useful property (of a cell) when choosing a cell type for heterologous expression of a channel?

should not express the channel already, should be eukaryotic so thatpost-translational modifications wold be the same

"Human ether-a-go-go." Why would mutants be considered to be conditional when they were first found in Drosophila?

shaking only seen under ether anesthesia

How does the shaker protein detect voltage?

S4, with it's positive charges, rotates

Why would the electric organ of the electric eel be better than the squid giant axon for cloning the sodium channel?

expresses plenty of channel

Give one of the three possible membrane compartments where calcium channels would be important in muscle contraction.

pre-"synaptic" membrane, t-tbule, sarcoplasmic reticulum

Knowing about cystic fibrosis might help you to understand the channel for what neurotransmitter?

GABA

***Synapses

Why would pheochromocytoma cells be a reasonable model for studying neurotransmitter release?

can culture adrenal medulla cancer cells which release catecholamines

"Ramon y Cajal's 'cell theory' implies that something like a chemical synapse MUST exist (even though they has not been demonstrated yet)" Explain.

the alternate, Golgi's reticular theory, has continuous processes, while separate cells require communication between cells

Describe the structural or molecular specializations that form an "electrical synapse."

in gap junction, connexons are formed from hexamers of connexins in register from one cell to the next

"There are no inhibitory neuromuscular junctions in the vertebrate." What does that information tell us about "the final common pathway in the integrative action of the nervous system?"

it must be in the spinal motor neuron since there is no integration after that

What kind of technique would be needed to determine the reversal potentials for the IPSP and the EPSP?

voltage clamp

Activation of the nerve elicited (what? - be specific) at the end plate when Katz decreased the extracellular calcium ion concentration.

miniature end plate potentials, 0, 1, 2, or 3 of them

Describe either the freeze-fracture or the transmission electron microscope image of a vesicle in the process of release.

holes (pits), omega figures

Why would there be transporter molecules in the vesicle membrane?

to maintain a steep gradient against leakage

On the spinal motor neuron, there are synapses onto the dendrites and cell body. A picture was shown of the first synaptic area behind the Drosophila compound eye, and the point was made that invertebrate neuropils we would see later in the semester are similarly organized. How does this synaptic organization differ from that of the vertebrate?

the cell body of the postsynaptic neuron is on the outside of the ganglion, aloof from synapses

How could Shibire mutants have temperature sensitive paralysis when the mutation does not block vesicle release?

it blocks recycling of vesicle membrane

Why would a doctor give a patient a clostridial protease that cleaves synaptobrevin?

cosmetic dermatologists would discourage wrinkles in the face by blocking neuromuscular junctions

What is the target membrane that the vesicle-SNARE latches onto?

presynaptic

What nerve did Otto Loewi from Austria use in the first demonstration that a neurotransmitter substance was used in signaling?

vagus

A patch with hexamers in register between two adjacent cells describes what kind of intercellular communication structure?

gap junction

"The spinal motor neuron is the final common pathway in the integrative action of the nervous system." Why is the spinal motor neuron (as opposed to the muscle cell) the final place where integration of signals can take place?

there is excitation, no inhibition, on the muscle cell

Starting at a normal resting potential (not voltage-clamped), what happens to the membrane potential of the postsynaptic cell if a GABA-releasing presynaptic cell is activated?

it hyperpolarizes

A micropipette that was used to selectively inject chloride ions into neurons told us (what) about postsynaptic potentials?

IPSPs are based in part on an increase in chloride conductance

In Sir Bernard Katzís Nobel Prize-winning research, he turned end plate potentials into 0, 1, 2, or 3 miniature end plate potentials. Answer either (1) How? Or (2) Why?

(1) by decreasing calcium ions (2) to show that vesicles were the unit of synaptic transmission

Name a protein involved in retrieval of vesicle membrane.

clathrin dynamin

After calcium ions come in through channels in the presynaptic membrane, it binds to a calcium-binding protein to mediate vesicle release. Answer either (1) What is its name? or (2) Where is it (which specific compartment involved in vesicle release)?

(1) synaptotagmin (2) bound to vesicle membrane

Why do they refer to "omega figures" in the ultrastructure of synapses?

vesicles in the process of release are shaped like Greek letter omega

What kind of synapse involves opening of a chloride channel?

inhibitory

Suppose you voltage clamp a postsynaptic neuron to a level negative to the reversal potential. What would you record (postsynaptically) if you activated a cell making a GABAergic
synapse?

in this case it would depolarize

Name a protein involved in recycling of synaptic vesicle membrane.

clathrin, dynamin

What is the quantum of transmission that Katz found to elicit a miniature end plate potential of 0.4 mV?

vesicle

Compared with the conductance of a voltage-gated ion channel, what is the conductance of a one gap junction channel?

huge

What happens to the conductance of the postsynaptic menbrane during the EPSP?

it increases

What is a connexin used for?

gap junction

How does Ca2+ get into the cell to affect vesicle release?

through a calcium channel

What do the clostridial toxins from anaerobic bacteria do?

cleave Synaptobrevin / VAMP (vesicle-associated membrane protein) = v-SNARE, inhibit vesicle release

Katz was interested in the end plate potential. Where is the end plate?

the "post-synaptic membrane" of the muscle cell

Two SNAREs hook onto eachother, v-SNARE and t-SNARE. What are v- and t-?

vesicle and "target" (presynaptic membrane)

What happens to the end plate potential when extracellular Ca2+ is decreased?

gets small

Why do tetanus and botulinum toxins have opposite effects on motor activity?

both inhibit vesicle release, tetanus is in inhibitory interneurons

What would not happen at the restrictive temperature in a temperature sensitive mutation affecting the protein dynamin?

coated pits would not pinch off to vesicles

Why did Sherrington consider the spinal motor neuron rather than the muscle cell itself to be the "final common pathway" of "the integrative action of the nervous system?"

because it receives + and - inputs while the muscle only gets + input

What happens to the conductance at the postsynaptic ionotropic receptors for K+ and Cl- for the IPSP?

they go up

Not just any old Ca2+ channel would work on the presynaptic membrane. It has to be voltage gated. Why?

to detect the arrival of the action potential

What are connexin proteins, such as Cx36, used for?

gap junctions

With extremely low extracellular Ca2+, why would the potential recorded at the end plate be several different sizes for several different nerve stimulations?

because you might get o, 1, 2, ... miniature end plate potentials

What does parasympathetic output via the vagus do to the heart rate?

slows it

The toxin from Clostridium botulinum (BoTX) cleaves an important protein. Precisely where is this protein localized?

on the vesicle

Why are vesicles in the process of release sometimes called omega figures?

a TEM of it is shaped like the Greek letter

Electrical "synapses" use what membrane specialization in common with heart muscle cells?

gap junctions with connexons made up of connexin protein

What happens to the conductance of the postsynaptic membrane when GABA (gamma amino butyric acid) elicits an IPSP (inhibitory postsynaptic potential)?

increases (for potassium and chloride)

"Activating the corticothalamic path causes long-term decrease in electrical synapse strength." These electrical synapses are made of what protein?

connexin

Why did the Nobel prize winning Sir Charles Sherrington refer to the vertebrate spinal motor neuron as "the final common pathway in the integrative action of the nervous system?"

there can be no integration (of + & - inputs) further out since each muscle cell has only (one) + connection

Graded depolarizations and hyperpolarizations on the dendrites and cell body pool. As a result, an action potential is initiated (where)?

Axon hillock

Determining reversal potentials was instrumental in establishing the conductances mediating the EPSP and IPSP (excitatory and inhibitory postsynaptic potentials). What was done, in addition to Voltage clamping and recording from the postsynaptic membrane, to determine the reversal potentials?

stimulate the presynaptic neuron

With very low Ca2+, upon stimulating the motor neuron's axon, the end plate potential (EPP) was usually 0.4, 0.8, 1.2, etc mV. What other size was observed?

zero

Recycling of vesicle membrane begins with a clathrin coated pit. A mutation of what protein prevents the pit to pinch off to a vesicle?

dynamin (the shibire gene product)

There are synaptic connections to the dendrites and cell bodies of vertebrates. How is the situation strikingly different for invertebrates?

cell bodies are on outside of neuropil, away from where connections are

If heat resistant bacterial endospores survive improper canning, by what mechanism would eating those tomatoes affect transmitter action?

bacterial botulism toxin would cleave synaptobrevin (v-SNARE)

Give one of the several reasons why alumni Michelle Li, also Johnnie Moore, used PC12 cells in their published research.

they release catecholmines

Compare the conductance of a gap junction channel with that of a potassium channel.

way higher

What's with the "36" when they call the gap junction protein in the thalamus "Cx36?"

molecular weight

How did Nobel Prize winner Loewi prove that a substance released by the vagus slows the heart?

solution bathing heart slowed by vagus stimulation slows another heart

What property of the neuromuscular junction rationalizes Sir Sherrington referring to the spinal motor neuron as "the final common pathway" of "the integrative action of the nervous system?

since there is only excitation at the vertebrate n.m.j, the motor neuron is the last place excitation and inhibition can integrate

If you observed a coated vesicle near a synapse, say whether it is in the process of exocytosing and justify your answer.

no. endocytosing, those are the pits with clathrin

Relate vesicle release with either (1) improperly canned goods, (2) dangers of terrorism against civilians, or (3) facial cosmetic treatment.

BoTox decreases release, form heat resistant endospores turning into anaerobic bacteria that make a potent toxin that can be injected to decrease face wrinkles

Why, in Sir Bernard Katz's Nobel Prize-winning experiment, did they refer to "end plate potentials" instead of "postsynaptic potentials?"

neuromuscular junction was used to model a synapse

"Silencing of synaptotagmin in PC12 cells inhibits Ca2+-evoked catecholamine release." Why does calcium elicit release if synaptotagmin is not inhibited?
 
Calcium, coming in through calcium channels, mediates vesicle release

Consider the mepp (miniature end plate potential) and answer either (1) What cellular mechanism delimits it to be way smaller than the full end plate potential? Or (2) Suppose your preparation were giving you just a few mepps on the average ­p; what would you do to the preparation to restore the full end plate potential?
 
Fewer vesicles are released with low extracellular calcium, add calcium
 
There are synaptic connections to the dendrites and cell bodies of vertebrates. How is the situation strikingly different for invertebrates?
 
Synapses are in a neuropil(e) and cell bodies are on the outside of ganglia
 
At first they were surprised that a mutation in dynamin (shibire) would exhibit paralysis when moved to the restrictive temperature. Rationalize why.
 
If vesicle membrane fails to recycle, eventually vesicles would not be released
 
"Botulism and tetanus toxins cleave synaptobrevin." Precisely what membrane is synaptobrevin on?
 
vesicle

***Transmitters
 
How is Met-enkephalin produced from pre-proenkephalin A?

it is cleaved from the larger protein

Blocking the muscarinic cholinergic receptor on the heart with atropine would save your life if you were poisoned with what class of molecules?

acetylcholinesterase inhibitors

How is a norepinephrine breakdown enzyme an important target in the pharmacology of treatment for depression?

norepinephrine is obviously an "upper", so potentiating its action by inhibiting its breakdown would certainly be uplifting

"The nicotinic receptor is ionotropic." Translate: What is the transmitter? What is the molecular structure of the receptor? (Answer both.)

acetylcholine gates a channel

While administering Prozac to a patient with depression, the doctor needs to closely monitor (what?).

any suicidal thoughts or actions

In order to produce hamsters with large vs small testes, what did the lab prep technician need to do ahead of time?

put some on cycles of 8 hrs lights on vs 16 off and vice versa for the others

While light stimulates tells small-headed animals whether it is day or night, how is the pineal informed about the light-dark cycle in people?

input from the suprachiasmatic nucleus

Give one of the two possible reasons a diet high in tryptophan might make you sleepy.

precursor to serotonin and to melatonin

"Reuptake into the nerve terminus terminates the synaptic action of glutamate." How else is glutamate's action terminated?

it is also taken up into glia

What is sent throughout the brain from the Raphe nucleus?

serotonin

A symptom of Parkinson's disease is bradykinesia. What is bradykinesia?

not moving much

Explain either (1) why schizophrenia was once attributed to a serotonin defect, or (2) why this hypothesis was later excluded.

an LSD trip seemed like psychosis and LSD affected serotonergic transmission, bur amphetamine induced psychosis was more similar to schizophrenia

How did your professor rationalize that action potentials would be smaller in manic-depression patients who are on lithium therapy?

the gradient of lithium plus sodium, seen by the channel, would not be as steep because the pump cannot pump lithium

Phosphatidylinositol and phosphatidylethanolamine, precursors for endogenous cannabinoids, are supplied from what compartment in the cell?

membranes

"Tetrahydrocannabinol (THC) binds to CB receptors to mediate the effects of marijuana." Regarding the endogenous transmitters, answer either (1) Characterize the chemical PRECURSOR of one of these transmitters. Or (2) Where (in the cell) would this PRECURSOR be found?

membrane phospholipid, membrane

What is the general term for a pharmacological agent that mimics the action of an endogenous neurotransmitter?

agonist

For peptide transmitters, it is thought that vesicles are transported out the axon. In contrast, what goes out by anterograde axonal transport for small molecule transport like amines?

enzymes

Opium is not a neurotransmitter. Name an endogenous molecule functionally related to opium that is a transmitter.

endorphin or enkephalin

You were introduced to the function of the small G protein ras.in vesicle release. In contrast, how is the larger, heterotrimeric G protein involved in neurotransmission?

metabotropic receptors like the muscarinic acetylcholine receptor are 7 transmembrane spanning G protein linked receptors that signal to this G protein.

Reuptake is the standard mechanism for the termination of neurotransmitter action. In contrast, how is the action of acetylcholine terminated?

breakdown by acetylcholinesterase

To study what type of neurotransmitter did a neuroscience course alumna use pheochromocytoma (PC) cells?

Why is the color of the substantia nigra related to the neurotransmitter it produces?

DOPA is the common precursor of melanin and dopamine

Potentiating the action of (what?) is the rationale for the use of inhibitors of MAO (monamine oxidase) as antidepressants.

since norepinephrine is not metabolized, there is more of it

Acetylcholine and nicotinic receptors are used in parasympathetic ganglia. What transmitter and transmitter receptor would you find at sympathetic ganglia?

same

One portion is called thoraco-lumbar. What is the equivalent name for the other portion (of the autonomic nervous system)?

cranio-sacral

Where does the nitric oxide (NO) responsible for smooth muscle relaxation come from? (cell type or enzyme)

endothelium, eNOS (endothelial nitric oxide synthase)

Cyclic GMP's breakdown is inhibited by what drug (or class of drugs)?

Viagra (Levitra Cialis) ED meds

"Now that there are antidepressants, there is no reason to be depressed." Then why is there so much controversy about drugs like Prozac (and Paxil and Zoloft)?

some critics implicate them in increased risk of suicide or homicide

Melatonin... (answer either) (1) ...is synthesized from what transmitter? Or (2) ...is synthesized in what part of the brain?

(1) tryptophan (2) pineal

"Testes of short day hamsters are smaller than testes of long day hamsters" because of what hormone?

melatonin

For glutamate and GABA, what mechanism supplements reuptake into the nerve terminal to terminate the action of the transmitter?

reuptake into glia

GHB (gamma hydroxy butyrate, the infamous date rape drug) is related to transmission by what neurotransmitter?

GABA

Why does it take a lot of DOPA to treat Parkinson's disease?

very little is available to cross the blood brain barrier because the decarboxylase is everywhere

Receptor antagonists for what transmitter are considered to be the most effective treatment of schizophrenia?

dopamine

"People on lithium treatment might have smaller action potentials." Answer either (1) Why would some people be given lithium? Or (2) Why would their action potentials be expected to be smaller?

(1) to treat the manic phase of manic depression (2) b/c, since lithium does not get pumped out, the gradient of cations seen by the sodium channel is not normally steep

What is the common precursor for dopamine and melanin?

l-DOPA

In presenting the synthesis of glutamate, what cell is the source of the precursor, glutamine?

glia

SSRIs (selective serotonin reuptake inhibitors) are used to treat what disorder?

depression

What is the source (location) of serotonin that is spread widely through the brain?

Raphe nucleus

l-aromatic acid decarboxylase, used to convert 5-HTP to 5-HT, also makes what other neurotransmitter?

dopamine

In which part of the nervous system is glycine widely used?

spinal cord

Where are the enzymes for norepinephrine synthesis?

in the terminal

The benzodiazepine tranquillizers (chlordiazepoxide = Librium, diazepam = Valium) affect transmission with what transmitter?

GABA

At the autonomic ganglia, what is the transmitter?

acetylcholine

From what transmitter is melatonin synthesized in the pineal?

serotonin

What transmitter is most closely related to the date rape drug?

GABA

How is POMT (proopiomenanocortin) processed to yield b-endorphin?

cleved

What transmitter from the sympathetic nervous system would speed the heart beat?

NE

What class of molecules serves as the precursor for endocannabinoids?

membrane phospholipids

What does NO=nitric oxide do to arteriole smooth muscle?

relax

On the news this week is the case of a defendent blaming the murder on Zoloft (the Zoloft defense). Why would he have Zoloft in his system?

for depression

"Thoraco-lumbar" is another term for what component of the nervous system?

sympathetic

Name two monamines synthesized from amino acids.

dopamine, norepinephrine, epinephrine, serotonin, histamine

Tell me about the vesicles for endocannabinoid transmission.

there are none

How is GABA different from the 20 amino acids coded in the genetic code and used as the building blocks of proteins?

NH2 and COOH are on different carbons

What is the difference in how acetylcholine and norepinephrine are cleared from the synaptic cleft?

ACh broken down, NE reuptaken

Dopamine beta-hydroxylase converts dopamine to norepinephrine. Discuss optical isomerization (l- vs. d-) for precursor and product.

dopamine lacks a carbon with 4 separate groups while there could be l- and d-NE (it is l- that we use)

The garden tomatoes were not cooked enough before being "canned" in mason jars. What would happen to your muscle contractions if you eat them?

botulism would block muscle activation by nerve vesicles

In addition to cranial nerves, what other nerves make up the parasympathetic nervous system?

sacral

"The parasympathetic nervous system dilates arterioles in the corpus cavernosum, mediating erection." Give either of the reasons that this statement is not the whole truth according to more modern research.

the parasympathetic ns actually works by inhibiting the sympathetic. Also, the NANC (non adrenergic non cholinergic)ns is predominant.

What would sympathetic activation do to the blood flow in muscle?

increase it, hyperemia, "pumpitude"

How would you get beta-endorphin from proopiomelanocortin?

proteins are chopped down to make peptide transmitters

"Muscarine is an agonist for the cholinergic receptor." Translate.

muscarine is a drug that would activate one type of synapse for acetylcholine

Refering to schizophrenia, in interview, Bob said "receptor subtypes are very important. Block them all ... and you can get a Parkinson like movement disorder. Block only certain subtypes ... and you get relief of symptoms without the movement disorders." Receptors for what transmitter?

dopamine

How do sodium channel and sodium pump respond when lithium ions are substituted for sodium ions?

lithium goes in through sodium channels but is not pumped out by sodium pump

What pineal hormone is implicated in the differing testes of long- vs. short-day hamsters?

melatonin

Talk about the regulation of release (vesicles?) for nitric oxide (NO).

made on demand by eNOS (endothelial nitric oxide synthase) and diffuses directly across 2 membranes into the "postsynaptic cell" to stimulate GC (guanylyl cyclase)

Excitotoxicity, and too great an influx of calcium ions, is caused by overstimulation of synapses for what transmitter?

glutamate

What is the standard treatment to increase dopamine in the striatum in Parkinson's syndrome patients with low dopamine from degeneration of dopaminergic neurons?

feed them l-DOPA

Histochemical fluorescence demonstrated a place in the brain that spreads norepinephrine throughout the brain. What is the name of this place?

locus coeruleus

Ritalin is given for ADHD which stands for what?

attention deficit hyperactivity disorder

What type of molecule is arachidonic acid and how is it related to endocannabinoids?

fatty acid, it is the major portion of the molecule

How does epinephrine differ from norepinephrine?

NE is sympathetic neurotransmitter, PNMT converts NE to E which is hormone from adrenal medulla

Before it was shown to be nitric oxide (NO), it was called "endothelial derived relaxation factor (EDRF)." What did it relax?

arteriole smooth muscle

Title of a published paper: "Localization of cholecystokinin to cells of the retina." What is a gut hormone doing in that part of the nervous system?

originally identified as a gut hormone, it has different functions in different places

Met-enkephalin and Leu-enkephalin are chopped out of what kind of molecule?

larger protein precursor

A neurotransmitter activates a G-protein-coupled receptor, and that signals to (what is next in the cascade)?

duh! G protein (the heterotrimeric kind)

Say something about l- vs d- in the synthesis of catecholamines.

start w/ l-aa. lose when DOPA to Dopamine. Back to l- when dopamine goes to epinephrine

"End-product inhibition regulates synthesis by controlling the rate-limiting enzyme." If norepinephrine is the end product, what is the rate-limiting enzyme?

tyrosine hydroxylase

By what mechanism would monamineoxidase (MAO) inhibitors relieve depression?

increase presence of norepinephrine

A hormone that is formed from serotonin by two additional enzymatic steps is produced in what brain structure?

pineal

While glycine is an inhibitory transmitter of the spinal cord, what is the main inhibitory transmitter in the brain?

GABA

Transporters in what two cell areas terminate the action of glutamate?

nerve terminal and glial cell

What would Prozac, Paxil or Zoloft do the the concentration of what transmitter in the synaptic cleft?

increase serotonin

When more acetylcholine is needed, vesicles are released. How is the "transmitter" NO (nitric oxide) increased when it is needed?

turn on endothelial nitric oxide synthase (eNOS)

What does output from a famous cranial nerve do to heart rate?

vagus slows heart

Where is the chain of sympathetic ganglia?

near spinal cord, on each side, in thoracolumbar area

Chronic chlorpromazine administration causes "extrapyramidal motor syndrome" which is like what named disease?

Parkinson's disease

Theories that defects in serotonin and norepinephrine metabolism cause schizophrenia were replaced with the current explanation involving what transmitter?

dopamine

What ion has long been used to treat manic-depression?

lithium

"Naloxone, an antagonist, displaced certain narcotic analgesics in brain binding." This finding led to the isolation of what kind of receptor?

the opiate receptor

In the synthesis of anandamide and 2-arachidonylglycerol (2-AG), answer one: either What class of molecules are the original precursors? OR What kinds of enzymes are used?

membrane phospholipids (phosphatidylethanolamine or phosphadidyl inositol), phospholipases

More important than monamine oxidase (MAO) and catechol-O-methyltransferase (COMT), how is the action of norepinephrine terminated?

reuptake

Considering the localization in the perikaryon of translation (protein synthesis) talk about the location of function of enzymes responsible for synthesis of norepinephrine and acetylcholine.

steps in terminal so anterograde transport from cell body

Tell me 2 of 3 products, fragments "chopped" from pre-proenkephalin A. Be very specific.

signal sequence, met enkephalin, leu enkephalin

Contrast the presence or lack of l- vs d- isomers for DOPA, dopamine, and norepinephrine.

dopa cold be l or d, also NE but dopamine's carbons do not have 4 separate groups

The white communicating ramus is on the way to (what?) and the gray communicating ramus is on the way from (what? - same answer).

sympathetic ganglion

Atropine affects the enteric nervous system to achieve (what?)?

decrease in gastrointestinal motility

Out of the four CNS locations from which autonomic nerves eminate, where is the origin of the nerves that mediate erection?

sacraol spinal cord

With respect to the corpus cavernosum, "norepinephrine contracts smooth muscle via alpha-1 receptors." What is the functional effect?

inhibit erection by decreasing blood flow through arterioles

NO activates guanylyl cyclase (GC) an enzyme whose product is (what?).

cGMP

I heard on a TV talk show "an enzyme in turkey makes you sleepy." Correct that incorrect statement, at least with respect to the conventional wisdom.

an amino acid, tryptophan, not an enzyme

In terms of regulation of neurotransmitter action, how does Prozac affect mood?

seretonin reuptake is inhibited

Melatonin is made (answer one of the following) (1) from what neurotransmitter? Or (2) predominantly in what part of the brain?

5HT (serotonin) pineal

How did they show that the Raphe nuclei send serotonin all over the brain?

histochemical fluorescence tract tracing, formaldehyde turned serotonin into a fluorescent product

The discovery that MPTP was a contaminant in a bad batch of heroin helped to develop an animal model to study (what?).

Parkinson's disease

What is bradykinesia?

decreased movement seen in Parkinson's

Although it sounds barbaric, electroconvulsive shock is still sometimes used for the treatment of (what?).

depression

Opiates displaced tritiated naloxone to help Pert and Snyder identify what molecule?

opiate receptor

Lysophosphatidylinositol is converted to 2-arachiconylglyceol, an endogenous transmitter related to what drug?

cannibis (marijuana)

"Acetylcholine is used in the sympathetic nervous system." Where?

at ganglia

In what way is the expression "putative neurotransmitter" distinguished from the meaning of the word neurotransmitter?
 
Putative implies that they are not yet convinced it qualifies as a neurotransmitter
 
Say something about how vesicles or enzymes for transmitter synthesis get from the cell body to the synaptic terminal.
 
Axon transport along microtubules
 
Beta-endorphin is cleaved from what protein precursor?
 
POMC
 
"Nicotinic acetylcholine receptor." Answer either (1) On precisely what membrane is it located at the neuromuscular junction? Or (2) What is the nature of its molecular configuration that leads its activation to generate a potential?
 
End plate (on muscle cell), it is a channel
 
Does Viagra function "upstream" or "downstream" of NO (nitric oxide) action? Explain your reasoning.
 
Since NO activates GC and Viagra inhibits cGMP PDE, downstream
 
Potentiating or inhibiting (which?) the action of a neurotransmitter (which one?) explains the action of Prozac.
 
An uptake inhibitor would potentiate seretonin
 
"Day length" (what fraction of a 24 hr period is illuminated) affects the size of the testes in a hamster by Answer either (1) What hormone? Or (2) From what brain structure?
 
Melatonin, pineal
 
Why does the neighboring glial cell have special significance for glutaminergic transmission?
 
Reuptake and delivery back to the neuron
 
Atropine affects the enteric nervous system to achieve (what?)?
 
decrease GI motility
 
Out of the four CNS locations from which autonomic nerves originate, where is the origin of the nerves that mediate erection?
 
sacral
 
In the cases of both norepinephrine and serotonin, a decarboxylase turns an amino acid into (what chemical class of molecules?).
 
amine (monamine)
 
When more acetylcholine is needed, vesicles are released. How is the "transmitter" NO (nitric oxide) increased when it is needed?
 
Activation of enzyme (NO synthase)
 
"Acetylcholine is used in the sympathetic nervous system." Where?
 
At the ganglion
 
The discovery that MPTP was a contaminant in a bad batch of heroin helped to develop an animal model to study (what?).
 
Parkinson's disease
 
l-DOPA Answer either (1) Why do you need to give a lot of it? Or (2) Why do you give that instead of dopamine? (for Parkinson's)
 
because it gets decarboxylated everywhere, dopamine does not cross the blood brain barrier
 
"Lesions of the lateral hypothalamus result in a thinner rat." In what way does this story relate to Parkinson's disease?
 
Loss of affect (motivation) results from disrupting dopaminergic tract
 
Explain why action potentials might be smaller if lithium were given?
 
Since lithium is not pumped but does go through channels, the gradient of sodium plus lithium is less steep
 
What is the general class of molecules that serve as the precursor of "endogenous tetrahydrocannabinol?"
 
membrane phospholipids

***Transmitter receptors

What is in the tail of Torpedo that made it useful for cloners interested in the nervous system?

lots of tissue with acetylcholine receptors

Why do you need to be very careful when you use muscle relaxation in conjunction with anesthesia?

while it is important for your patient or your research animal not to move, you must not paralyse without blocking pain

There is a muscle disorder where miniature end plate potentials are smaller than they should be, and it is not because the vesicles do not have enough acetylcholine. Answer either (1) What is the disorder? or (2) Why are the potentials smaller?

myasthenia gravis, fewer nicotinic receptors

Why would you give someone a beta blocker?

to decrease blood pressure at the level of beta adrenergic receptors in the heart

Phospholipase C converts a membrane phospholipid into (name or abbreviate one of the two).

IP3 or DAG

Why is caffeine an "upper?"

norepinephrine and epinephrine action is potentiated since the second messenger's breakdown by cAMP phosphodiesterase is inhibited

A poisonous snake, the banded Krait (Bungarus) bites its prey. Answer either (1) What effect does the venom have on the prey? (2) It has this effect by binding what specific neurotransmitter receptor? Or (3) Where are these affected receptors located?

paralyse, nicotinic, neuromuscular junction

A extensive table with all the possible components for ionotropic receptors for lots of neurotransmitters was shown to you. Why were dopamine and norepinephrine not on this table?

there are no channel receptors for dopamine or norepinephrine

The NMDA receptor (answer either) (1) is for what transmitter? Or (2) passes sodium, potassium and (what other important ion?).

glutamate, calcium

Answer either: The second and third cytoplasmic loops (and what terminal?) of the beta adrenergic receptor interact with (What is the next downstream molecule in this cascade?).

C terminal, G protein

The activated alpha subunit activates adenylyl cyclase. Answer either (1) Why would you expect it to remain attached to the inside of the membrane? Or (2) What has to happen before the activated alpha subunit reassociates with the beta-gamma subunits?

it is bound to the membrane, it turns ATP into ADP

"In this situation, atropine would save your life." What situation? And why would it save your life? (Answer both.)

poisoning with malathion, block acetylcholine receptors on tyhe heart, prevent it from stopping

"IP3 is a ligand for a channel." Answer either (1) For what ion? Or (2) On what membrane?

calcium, smooth endoplasmic reticulum

Whereas cAMP is known for actions such as gating a channel, it can also regulate the transcription of DNA into mRNA. Name one of the proteins intermediate between cAMP and RNA polymerase.

PKA, CREB

Caffeine inhibits what enzyme?

PDE

What would 125I - labeled a-bungarotoxin label?

the nicotinic receptor on muscle

What is the next in line downstream of the metabotropic glutamate receptor?

G protein

Describe, in terms of chemical structure, how cAMP interacts to activate PKA (protein kinase A).

4 cAMPs bind 2 inhibitory subunits releasing catalytic subunits

Linda B. Buch and Richard Axel won the 2004 Nobel Prize for discovering the nature of the olfactory receptor. What type of molecule is it?

G rotein coupled receptor

In what way is the nicotinic receptor different for muscle vs. neurons?

different subunits for pentamer

The Nobel laureate Earl Sutherland is considered the founder of signal transduction and is associtated with identifying what "second messenger" for adrenergic transmission?

cAMP

What is the transmitter for the NMDA (N-methyl D-aspartate) receptor?

glutamate

Why is atropine from deadly nightshade called "belladonna alkaloid."

women used pupil dilation to look beautiful

What would you give a patient with myasthenia gravis to relieve the symptoms?

neostigmine

Give the name (that relates to the pharmacological agonist) for the ionotropic (channel) receptor for acetylcholine.

nicotinic

Inositol trisphosphate is a ligand for what kind of channel located where?

calcium on reticulum

"Atropine could save your life if your heart were stopping from Malathion poisoning." This relates to what type specific receptor on the heart (name should include pharmacological agonist plus neurotransmitter)?

muscarinic acetylcholine

"Transgenic mice in which a Purkinje cell-specific promotor drove expression of a molecule that inhibits PKC lack LTD for the conditioned eye blink." Explain the significance, including what is PKC and LTD.

This was a way to show that protein kinase C mediated long term depression, a model of synaptic learning is a specific cell type, the Purkinje cell

A vesicle contains a pretty standard amount of acetylcholine. Then why is the mepp (miniature end plate potential) smaller in myasthenia gravis?

there are fewer nicotinic receptors

How do you make an NMDA receptor from subunits NMDA-R1 and NMDA-R2A through NMDA-R2D?

Lots of possibilitits since receptor is a multimer (4 or 5) mixed from that list

The lecture and outline indicated that "the second and third loops and C terminus are for interaction with the alpha subunit of heterotrimeric G protein." Loops and C terminus of what type of protein, and where, in the cell's topology, are the loops and C terminus?

G protein coupled receptor is on membrane and those places are, obviously, on the cytoplasmic side

In the G protein signal transduction cascade, which specific molecule or subunit has GTPase activity?

alpha subunit of heterotrimeric G protein

Where does CREB (cAMP response element binding protein) bind, and what does it do by binding there?

promoter, affect transcription

How does caffeine have its stimulatory effects?

inhibits cAMP phosphodiesterase

In the good old days (1980's), gene cloners started with a tissue that expressed the gene product abundantly. What was this tissue for the nicotinic receptor?

electric organ of Torpedo

Why would you use alpha-bungarotoxin labeled with radioactive iodine in research?

label nicotinic receptor

Curare is most famous for blocking (what specific kind of receptor) in (what specific location)?

nicotinic motor end plate

For ionotropic receptors, e.g. NMDA receptors, there are "a large number of receptor isoforms." Why?

many possible subunits in many different conformations

Librium, Valium and barbiturates bind to subumits of (what type of receptor) for (what transmitter)?

GABA

What drug slows the termination of cAMP activity and how?

caffeine blocks cAMP phosphodiesterase

"The beta blocker Propranolol is used to treat hypertension." What is the neurotransmitter whose receptor is blocked and where?

norepinephrine, SA node

Why would you think, even before it had been shown, that the N-terminal part of the G protein coupled receptor was not the part that binds the G protein?

it must be on the outside of the membrane

Atropine causes the pupil to dilate. With that hint, tell me what part of the nervous system, using what transmitter, causes the pupil to constrict.

parasympathetic, acetylcholine

The alpha subunit of the heterotrimeric G protein has GTPase activity. Why is that important?

to terminate its action

IP3 causes an increase in cytosolic Ca2+. How?

bind IP3 receptor (Ca2+ channel) in smooth ER

It takes 4 cAMP molecules to activate PKA. How (biochemically) do they do that?

2 each bind and remove 2 inhibitory subunits from 2 catalytic subunits

In the cAMP pathway, protein kinase A (PKA) can phosphorylate CREB (cAMP response element binding protein). What type of molecule does CREB bind to?

DNA

How would alpha bungarotoxin help the snake get its prey?

paralyze

What is missing and where in myasthenia gravis?

nicotinic receptors at end plate

Some anesthetics, Valium, and barbiturates affect what kind of receptor for what neurotransmitter?

channel for GABA (GABA-A receptor)

With dopamine as the ligand and the inhibitory G protein, what happens to the level of what famous "second messenger?"

cAMP goes down

The blind Drosophila mutant norp A has no photoreceptor potential and lacks phospholipase. Name either one of the two products of this enzyme or the precursor. Abbreviations will suffice

PIP2 -> IP3 + DAG

Torpedo was useful Answer one (1) To do what? (2) Why was it particularly useful?
 
Clone the acetylcholine receptor, which is plentiful in T's electric organ
 
What would you use radioactively labeled (125I) alpha-bungarotoxin to do?
 
To isolate the acetylcholine receptor
 
Anesthetics, benzodiazepines and barbiturates affect the GABA-A receptor. Describe or draw what this receptor looks like.
 
channel
 
Describe or draw what a dopaminergic receptor looks like.
 
G protein coupled receptor crosses membrane 7 times
 
Related to adrenergic receptors, answer either (1) Why would an alpha agonist unstuff a stuffed nose? Or (2) Why would a beta antagonist help alleviate hypertension?
 
Stimulate arteriole (precapillary sphincter) smooth muscle, decrease rate and contractility of heart
 
Why would atropine save your life if you were dying of acetylcholinesterase inhibitor poisoning?
 
Block muscarinic receptors that are making the heart stop when there is too much acetylcholine
 
Tell me one of the things the alpha subunit of the G protein does when it is activated by binding GTP.
 
Dissociate from beta-gamma, activate the next molecule in the cascade, break down GTP
 
When a G protein signals to PLC (phospholipase C), answer either: (1) What is the next effect for one product of that enzyme (DAG=diacyl glycerol)? Or (2) What is the next effect after the production of the other (IP3 = inositol trisphosphate)?
 
DAG activates protein kinase C, IP3 is the ligand for a calcium channel on an intracellular cistern (smooth ER) of calcium
 
For cAMP answer either: (1) How, molecularly, were 4 cAMP molecules used to achieve their effect? Or (2) What drug would keep cAMP present for a longer amount of time?
 
Two each bind to and remove 2 inhibitory subunits from two catalytic subunits, caffeine or theophyline

How does a famous "second messenger" activate protein kinase A (PKA)?

4 cAMPs bind 2 inhibitory subunits and pull them off of 2 catalytic subunits

With the assistance of CREB (cAMP response element binding protein), Answer either (1) what enzyme acts on (2) what macromolecule to medeiate transcription.

RNA polymerase acts on DNA

***Neuroanatomy

With your "orange stick," you scrape all the gray matter out of one sulcus. Answer either (1) How can you tell what direction the myelinated axons run? or (2) Where do the first axons you find come from and go to?

stick glides in axon direction and scrapes across the grain, from and to the adjacent gyri

In the corticospinal tract, these motor cells in the precentral gyrus make their first synapse (where?).

to the spinal motor neuron in the ventral horn

You have a rat brain atlas and your anesthetized rat (in an approved protocol) is mounted in a stereotactic device with the skull exposed. Say something about what you need to do to get the tip of an electrode into the ventromedial nucleus of the hypothalamus.

measure from the bone sutures*, drill a hole, lower the electrode to the correct depth*, *=requires consulting the atlas

Before Pruissinger's prion hypothesis... answer either (1) What kind of disease? was explained by Nobelist Gadjusec by a virus? (2) A virus with what special kind of properties?

spongiform encephalitis, CJD, kuru, etc.; slow

The medial forebrain bundle goes through the lateral hypothalamus and includes [answer either] (what famous tract?) that is disupted in (what disease?).

nigrostriatal tract, Parkinson's

What do you have to cut off to see the floor of the fourth ventricle?

cerebellum

The left side of the cerebellum controls which side of the body?

left

"Massa intermedia" is an operational term for what major relay structure in the brain?

thalamus

If you miss the midsagittal cut a tiny bit... Name one of the three tracts you would see where the thalamus is located.

fornix, mamillothalamic tract, habenulopeduncular tract

For questions 10-13, see this figure

10. Name this structure (or give it's cranial nerve number)

olfactory bulb, I

11. This white matter is seen in the midsaggital view as... (name either of the two tracts).

fornix, hippocampal comisure

12. What is this artery that feeds the circle of Willis?

internal carotid

13. What is this structure?

lateral geniculate nucleus (thalamus)

For questions 14-21, see this figure

14. These fibers, hidden as they pass under the pons, form what tract?

corticospinal, pyramidal

15. Here it is called the pons. What do you call these fibers, on the "other side," in the dissection of the 3 components of the cerebellar peduncle?

brachium pontis or middle cerebellar peduncle

16. This one nucleus is in a system with two others. Name one of the two OTHER nuclei.

putamen, globis pallidus

17. What is the frog's equivalent of this structure?

optic tectum

18. What is this major body of white matter called?

internal capsule

19. What was revealed after you removed this important limbic structure wrapped in myelinated axons (i.e. under the structure you removed)?

thalamus

20. The brains provided for your dissection still had this white "membrane" (called what?) that you were required to remove before proceeding.

dura mater

21. For this figure, answer either (1) What is it called when the entire white matter under the cortical layers is exposed? or (2) What is the term used for these particular axons?

corona radiata, arcuate fibers

How did Pruisinger propose that a protein (without DNA or RNA) can be infectious and alter the proteins in the victim, making those proteins infectious.

protein in scrapie configuration converts protein in control configuration into the scrapie form

Other than cerebral cortex, name a major component of the telencephalon.

basal ganglia, hippocampus, olfactory bulb, basal forebrain

The oculomotor nerve (cranial nerve #3) has strictly motor function. State one of the other motor functions (other than connections to striated muscle associated with the eye).

accomodation, pupillary reflex

For striatum or lenticular nucleus, explain how the body got its name.

striated because of branches of internal capsule, shaped like a convex lens in horizontal section

(for # 15-19) go here

15. Give a name, number or function of the cranial nerve indicated.

occulomotor, 3, eye movement, pupil, accomodation

16. Give the function (for both) or a name (for either) area of white matter indicated .

outgoing voluntary motor tract, trapezoid body, trapezoid body

17. What is this white area called?

pons

18. Answer either (1) What is this structure called? Or (2) Say one of the things you would see if you removed that structure.

septum pellucidum, head of the caudate and lateral ventrical

19. What is this area called?

hypothalamus, third ventrical

(#s 20-24) go here

20. What is this white matter called?

internal capsule

21. What is this large structure in the middle of the brain called?

thalamus

22. What is this white matter called?

corpus callosum

23. What is the white matter on the outside of this structure called? (Alternatively, you could say one of the tracts on the midsagittal slice you see that are formed from these axons.)

fimbria, fornix, hippocampal commisure

24. What white matter is being ripped here?

(#s 25-29) go here

25. What kind of information is being carried by this tract?

olfactory

26. What is this cross-over structure called?

optic chiasm

27. What is this large area of the brain called?

cerebellum

28. You definitely saw this huge nerve in your dissection (pointed to twice). Give a name or number. Hint: there are 3 branches coming in from touch sensation in the the face.

trigeminal, 5

29. What is the name associated with the gray matter you needed to scrape away (from the mid-sagittal plane) to reveal this tract?

massa intermedia, thalamus

For Questions 1-8, refer to these pictures

1. Although it is operationally named the "massa intermedia," it is actually (what specific part of the brain?).

thalamus

2. What is this conspicuous white structure seen in mid-sagittal section?

optic chiasm

3. From a different perspective, you peeled off the hippocampus and saw this. Answer either (1) What is it called (specifically)? Or (2) What (functional) system is it part of?

lateral geniculate nucleus of the thalamus, visual

4. From a different perspective, you saw this structure hiding in the lateral ventricle behind the septum pellucidum. What is it?

head of the caudate nucleus

5. What is the name of this colossal body?

duh, corpus callosum

6. The hippocampus, shown here, is associated with white matter over its surface plus two tracts that can be seen in (or near) mid-sagittal section. One of those three would suffice for the answer.

fimbria, fornix, hippocampal commisure

7. A structure associated with the visual system is here. Answer either (1) What is it called in the sheep? (2) What is it called in the frog? Or (3) In combination with a nearby auditory structure, both bilateral, what name indicates this foursome?

superior colliculus, optic tectum, corpora (lamina) quadrigemina

8. When you cut off the cerebellum and looked at the floor of the fourth ventricle, what was this structure called (viewed from that perspective)?

brachium pontis of the cerebellar peduncle

Look here for 9-12

9. You can see this tract of white matter on the ventral surface of the brain. What system is it part of?

10. Suppose I'm pointing to the diencephalons, not the ventricle. What part of the diencephalons is this?

hypothalamus

11. This and the nearby tracts and the associated gray matter are part of a major subdivision of the brain collectively called (what?).

cerebellum

12. Which nerve controlling extraocular muscles has been cropped out?

occulomotor (III)

13. Your animal care protocol is approved. You have your anesthetized rat in the stereotaxic device and you have exposed bregma and lamda. What else do you need to aim an electrode tip to the ventromedial nucleus of the hypothalamus?

a rat brain atlas

14. How come you do not have spongiform encephalitis even though you have the protein in your brain, and even though you could contract spongiform encephalitis if exposed to tissue from a person or animal that does?

the protein would need to be changed to the diseased configuration (scrapie) from the normal configuration (control)

15. You are looking at the outside of the brain. Name a structure from the prosencephalon that you cannot see.

basal ganglia (any of them), hippocampus, internal capsule

16. 'The cranial nerves have sensory and motor functions. Regarding motor functions, they can be either for the (list both) motor systems."

autonomic & somatic

17. "The thalamus is a 'relay' for " Complete that sentence for both general functions.

sensory and somatic motor



For questions 1-5, refer here

1. The dissection reveals the brachium pontis, the brachium conjunctivum and Answer either (1) the third part. Or (2) the whole structure (all three put together).

restiform body (inferior cerebellar peduncle), cerebellar peduncle

2. Rostral to the above, in the midbrain, is the lamina quadrigemina. Answer either (1) the function of the inferior pair. Or (2) the function of the superior pair.

auditory center, visual center

3. Answer either (1) name or number of this nerve. Or (2) a specific function other than somatic motor control.

occulomotor (III), autonomic (pupil and accomodation)

4. What is the artery that feeds the circle of Willis?

internal carotid

5. Answer either (1) What is the function of the axons you see here? Or (2) What is the name given to the structure delineated here?

(pyramidal) motor system (corticospinal tract), trapezoid body

For questions 6-11, refer here

6. If you could see through the optic chiasm, what diencephalic structure would you be seeing?

hypothalamus (suprachiasmatic nucleus)

7. Tracts branching from what huge white matter structure give rise to this striated appearance?

internal capsule

8. "Periaqueductal gray" where the aqueduct connects what two numbered ventricles?

3rd and 4th

9. Here's a place you've heard of. (hint, the site of action of N-acetyltransferase and hydroxy indole O-methyl transferase)

pineal

10. Looks like we missed "mid" in this midsagittal cut by a bit. What nucleus would we see in the lateral ventricle on the other side?

caudate

11. What is this white matter?

optic chiasm

For questions 12-15, refer here

12. What is this white matter?

internal capsule (corona radiata)

13. You had a difficult time peeling off this tough layer called (what?).

dura mater

14. In addition to the fornix, what white matter from the fimbria is found in this area?

hippocampal commisure

15. If we tear through this (what is this?), we will see (answer to #10).

septum pellucidum

16. You have a rat in a stereotactic instrument. How do you decide where to drill the hole through the skull to reach a specific location?

a stereotactic atlas tells you the location relative to (XY) bone suture (lamda and bregma) and depth (Z)

17. With a stereotactic instrument, you aim for the medial nucleus of the hypothalamus and make a lesion (and collect data on the animal's weight for a few months). How can you know whether you hit your intended target?

You must do histology on the brain to see if the lesion is near the intended target (as identified in the atlas)

18. Part of the human retina projects to the contralateral lateral geniculate nucleus. The other part projects to the (what?) lateral geniculate nucleus.

ipsilateral, duh

19. You can contract Creutzfeld Jacob disease by eating contaminated tissue. Why is the current hypothesis explaining the spread of such diseases so contradogmatic with respect to infectious diseases?

no nucleic acids are involved, only protein, and even here, it is conformation that is critical

20. Using a term such as "myelencephalon," where is the frog's optic tectum?

mesencephalon

21. There are sensory and motor functions for the cranial nerves. In addition to striated muscle control, what other kind of motor control do the cranial nerves subserve?

parasympathetic autonomic

22. "The thalamus is a major relay station" [yes, I know that is an oversimplification] "for the motor system and for (what?)."

sensory systems as they project to the cortex

23. Why is the medial forbrain bundle called bundle instead of tract?

It is a collection of different tracts with different functions traversing together

24. "When you dip your face in water, parasympathetic and sympathetic changes mediate the diving response" caused by sensory input from what nerve?

trigeminal (5)

25. "The fimbria forms the fornix" and also it makes (what big gray area?) look white.

hi[ppocampus

26. Answer one of these: (1) Why would you need to use a different method of lesioning to study the behavioral effects of lesions of the hippocampus (compared with, say, the ventromedial nucleus of the hypothalamus). Or (2) how would you do such lesioning?

(1) it is huge, (2) use suction (or a lot of electrolytic lesions

27. What, specifically, takes up more space in the cervical and lumbar enlargements?

spinal motorneurons

28. What is the function of the choroid plexus?

secrete cerebrospinal fluid

29. The brainstem is considered to be the midbrain, the medulla, and (what?)

pons

30. The more conventional name for the archipallium.

hippocampus



For 1-16, refer to Figs 1st p, 2nd p, 3rd p, 4th p,

1. The name of this bulge.

pons

2. The name of this blood vessel feeding the circle of Willis.

internal carotid artery

3. The name of this ventricle.

3rd

4. The name of this nucleus. Its function. (two points)

caudate, motor (extrapyramidal

5. The name of this tract.

fornix

6. What big tract is being ripped here?

internal capsule

7. The name of this structure.

hippocampus

8. What part of the thalamus is this?

lateral geniculate

9. The name of this whole tract that is teased into 3 components on the other side.

cerebellar peduncle

10. Name one of the two nuclei that form this lens-shaped nucleus.

ptuamen, glogus pallidus

11. The name of this bulge. The name of the equivalent structure in the frog. (2 points)

superior colliculus, optic tectum

12. The name of this big bundle of cross over axons.

corpus callosum

13. The name of this bulge. Its function. (2 points)

precentral gyrus, motor

14. The name of this major subdivision of the brain.

cerebellum

15. The name of this small bundle of cross over axons.

anterior commisure

16. The name of this major subdivision of the brain.

medulla

Using a stereotaxic atlas of the rat brain and a stereotaxic apparatus, what do you measure from on the rat's head to find a defined brain location like the ventromedial nucleus of the
hypothalamus?

bone sutures bregma and lambda

Why do they call part of the basal ganglia the "striatum?"

brances off the internal capsule make these nuclei look striped

Only one of the cranial nerves for eye movements is also part of the parasympathetic nervous system. Which?

occulomotor (III)

When you remove the cerebellum, you are looking at the floor of which ventricle?

4th

The hippocampus looks white because of axons of the fimbria that form what major tract?

fornix

Among the meninges (brain membranes), which is the toughest?

dura mater

When Stanley Pruisinger, who eventually won a Nobel Prize, proposed the prion theory for spongiform encephalitis, how was he disagreeing with the Nobel Prize winning work
of D. Carleton Gadjusek?

SP said a protein could be infectious while DCG thought more traditionally that it was a virus (a slow one)

For questions # 1 - 4, refer to this figure.

1. This gray matter. Note that it is covered with white matter. Also note its location between the white matter of the cerebral cortex and the thalamus.

hippocampus

2. This thin midsagittal structure blocks your view into the lateral ventricle and the head of the caudate nucleus.

septum pellucidum

3. Part of the mesencephalon, this part of the lamina quadrigemina is a visual area related to the optic tectum of the frog.

superior colliculus

4. This bulge, white matter, leads to the brachium pontis of the cerebellar pecuncle. On the ventral view of the brain, it blocks your view of the pyramidal tract.

pons

for 5-8, see this figure

5. If you started cutting into the longitudinal fissure, what is the first white matter you would cut?

corpus callosum

6. This visual structure blocks your view to the supraoptic nucleus of the hypothalamus.

optic chiasm

7, Many of the brains we had for dissection showed this ribbon-shaped cranial nerve.

oculomotor nerve (III)

8. This tract is named for its connection from the thalamus to what specific portion of the hypothalamus, a body which would be conspicuous on the ventral view.

mammillary body

for 9-12, see this figure

9. This portion of the cerebellar peduncle has axons that are seen in what ventral structure?

pons

10. What commisure is here? (The arrow does not point to the corpus callosum.)

hippocampal commisure

11. What major subdivision of the brain is this?

cerebellum

12. Why is the hippocampus white?

its output axons, the fimbria, are on the surface

"Each picture in a stereotactic atlas of the rat brain is a coronal section with its distance anterior or posterior of bregma indicated." Translate.

coronal is dorsal-ventral, lateral-contralateral plane, and bregma is a landmark on the sutures of the bones

Why did I decide to tell the prion story in the neuroanatomy lecture before the brain dissection?

to give you a cautious appreciation for how contact with neural tissue, in the case of scrapie, might be dangerous

The pons covers up a white matter that goes from the cerebral peduncles through the pyramids. What is this tract (not the pons, rather the tract covered by the pons) used for?

motor output

The most obvious of the "membranes" (meninges) of an "un-peeled" brain is a very thick and tough one called the (what)?

dura mater

"Bundle," "capsule,""commisure," and "lemniscus" are all terms referring to what specific type of tissue?

tracts

Toward the bottom of the spinal cord, there are many parallel tracts. What is this called?

cauda equina

Sometimes caudate plus putamen is called striatum. Why?

looks striated from branches of white matter off the internal capsule

What vascular tissue, seen dark in dissection, secretes cerebrospinal fluid?

choroid plexus

For 1-3, see here

1. In some brains, this was intact, in others, it was damaged, revealing a fluid-filled compartment. What is it?

olfactory bulb

2. Hardly anybody had this good of a view of this pair of laterally projecting nerves found near the stump of this obvious rostrally projecting nerve. Give the name or number of one of them.

Facial (7) or auditory (8)

3. If this tract is followed laterally and superiorally, with the cerebellum removed, it is part of a huge structure of white matter. What is this white matter called?

cerebellar peduncle

For 4-8, see here

4. Here is white matter (covered by the pons). What is the function of this white matter tract?

motor (pyramidal [corticospinal] tract)

5. Between the two lines (and just on the other side of the optic chiasm) lies what structure, important in motivation?

hypothalamus

6. With the cerebellum removed, what are the midbrain structures seen

superior (and inferior) colliculi,, lamina (corpora) quadrigemina

7. and what would the visual counterpart be called in the frog?

optic tectum

8. What ventricle is this?

4th

For 9-12, see here

9. What motor nucleus is right on the other side of the septum?

caudate

10. What is the name of this huge area of white matter?

internal capsule

11. Covered by the hippocampus, what is the specific function of this part of the thalamus?

vilson (lateral geniculate nucleus [body])

12. The fimbria fibers that make this structure white are bundled together in what tract that can be seen in mid-sagittal section?

fornix

What distinguishes a bundle (like the medial forebrain bundle) from a tract?

several unrelated tracts travel together

What are the diencephalic structures that would be seen in the neighborhood of the third ventricle?

thalamus and hypothalamus

The surface of the hippocampus is white. How, during the dissection, would you ascertain the direction that these axons go?

stroke with the grain and across the grain with the cuticle stick

Starting at the lumbar area and going through the sacral area, describe the spinal cord.

cauda equina, a bunch of nerves

***Touch and pain

After C-type sensory afferents arrive in the spinal cord, the projection of this information ought to ascend in what portion of the spinal cord?

anterolateral

Why would you expect a Pacinian corpuscle to have a large receptive field?

since it is deep, deflection of a large area of skin would stimulate it

For either (1) Group I and II afferent axons or (2) Gamma motor neurons, state what is feeding into it (for 1) or what it feeds to (for (2).

stretch receptors, intrafusal muscles

Capsaicin stimulates the VR-1 receptor. Answer either (1) What would be the "normal" (biologically relevant) stimulus? (2) What related Drosophila mutant was discovered much earlier? or (3) Say something about the molecular structure of this receptor.

heat, transient receptor potential, channel

What is the difference between the gracile and cuneate tracts?

gracile is information from lower limbs, cuneate from upper

Why isn't the face included in the diagram of dermatomes?

trigeminal cranial nerve input is separate from segmented spinal cord input

In terms of axon type, what is the difference in the neospinothalamic tract vs the paleospinothalamic tract?

neo A delta, paleo C

Most pain from the lower body travels in the anterolateral tracts. For the exception, answer either (1) What kind of pain travels elsewhere? (2) Where does it travel?

viceral pain, dorsal columns

The two point discrimination threshold is 3 mm for the index finger and 45 mm for the calf. The tongue was not in the textbook figure, but you should be able to give me that number here.

probably about 3 like the finger

The trigeminothalamic tract carries what particular type of information?

touch, pain, etc from the face

Your coverage in this course gave you only one neuron that releases eckephalin. Where is it located?

dorsal horn, substantia gelatinosa

Stimulation of 9 square mm of skin affects one Merkl disk; by contrast, stimulation of 60 square mm of skin affects one Ruffini end organ. Thus the Ruffini has a larger (what is the expression?) than the Merkl.

receptive field

Feature detection is the expression for the processing of sensory input so that reduced information is passed along to the next higher level in the nervous system. Drawing an analogy to the visual system, I argued that it is easy to locate a gentle tap to the forearm even though all the flesh that jiggles is actually stimulated. What is the expression for the type of neural interaction that mediates this feature detection?

lateral inhibition

The afferent from a nociceptor has its cell body in the dorsal root ganglion. Where is the first synapse? (Answer both: location plus which side, using the appropriate term to answer which side.)

dorsal horn gray matter ipsilateral

Ia, II and A-beta are among the afferent axon types. Give me either [(1) the designation or (2) a specific function] of a slower afferent axon type.

A-delta, C, pain, temperature

For proprioception and the stretch reflex, give the specific name of either [(1) one of the two types of intrafusal muscle fibers, or (2) the fusimotor efferent axon].

nuclear chain or nuclear bag fiber, gamma motor neuron

A VR-1 receptor is a ligand-gated channel for which capsaicin is the ligand. Answer either: (1) What is the more natural stimulus that affects this channel? Or (2) What was the original member of this channel family called when it was discovered to be deficient in a Drosophila visual mutant?

warm, transient receptor potential

There is a synapse in the gracile or cuneate nucleus. Answer either (1) Where is the "beginning" of the cell that makes the synapse? Or (2) Name one type of receptor that sends information in on this pathway.

touch, in the skin, Merkl, Meisner, Ruffini, Pacinian, stretch receptor

The anterolateral system is for pain. There is a notable exception (in terms of spinal tract location). Answer either (1) What type of pain is carried in this exceptional tract? Or (2) Where in the spinal cord is it carried?

viceral, dorsal columns at midline

Tell me a place where the 2-point discrimination threshold for fine touch is less than 5 mm.

fingertips, lips, tongue

Name a transmitter used in a microcircuit in the dorsal (posterior) horn gray matter (substantia gelatinosa).

glutamate, enkephalin, substance P

Regarding receptive field, answer either (1) Why is the Pacinian corpuscle's receptive field the largest? Or (2) What units would you use to describe the receptive field of a touch receptor?

deeper in the skin, a greater area of deformation would stimulate it; square mm

Under what normal circumstance would your receptors that are specifically responsive to vibration be stimulated?

while running your fingers over a textured surface (active touch)

Gamma motor neurons (the fusimotor system) connects to (answer either) (1) What? Or (2) For what purpose?

intrafusal muscle, preset the stretch of the stretch receptor

For capsaicin, answer either (1) What does the receptor look like (molecularly)? (2) What would be the more normal way to stimulate this molecule? or (3)Tell where (or how) this type of receptor was first found.

a channel, heat, transient receptor potential phenotype of Drosophila led to mating defect

"In conclusion, a pain receptor is a chemoreceptor for (name a chemical)."

histamine, acetylcholine, serotonin, bradykinin

In the lemniscal system, a sensory receptor in the lower part of the body makes its first synapse (where)?.

gracile nucleus

In the sense of touch, neural processing takes place to sharpen spatial localization of the stimulus. What kind of neural processing?

lateral inhibition

As described by dermatomes, sensory receptors in the legs input to sacral and (what?) parts of the spinal cord.

lumbar

For the touch input from the face that travels in the medial lemniscus, answer either (1) What is the cranial nerve for input? Or (2) What is the specific part of the thalamus for synapses?

trigeminal (V), VPM

A cell in the dorsal horn of the gray matter of the spinal cord carries pain and temperature information to (where is the first synapse in?) the brain.

VPL (thalamus)

You were introduced to the term "neospinothalamic" whose input is from A-delta fibers. In comparison, answer either (1) What slower fibers have input for the more evolutionary ancient system? Or (2) What is this more ancient system called?

C fibers, paleospinothalamic

In general, pain from the lower body goes in the anterolateral system with (what exception?). [Note, the question still applies to the lower part of the body, i.e., not the face.]

from the viscera, via dorsal columns

Heart rate and blood pressure are changed substantially when a person dives into water. These changes can be mediated by fairly minimal stimulation with water. Answer either (1) What is that minimal part of the body that needs to be stimulated? Or (2) What is the nerve that carries that information to the brain?

face, trigeminal (V)

Compare the two-point discrimination threshold for the tongue vs for the forearm.

way smaller for tongue

Where did the Raphe nucleus get the sensory information to feed out to the cell in the dorsal horn of the gray matter of the spinal cord?

any of these will do: Somatosensory cortex -> amygdala and hypothalamus -> midbrain periaqueductal gray

For what specific aspect of mechanosensation would the rapid adaptation of Meissner's corpuscles be useful?

active (feeling) touch (of a textured surface)

Answer either (1) gamma motor neurons innervate what specific type of cell? Or (2) what is the function of this activation?

intrafusal muscle fibers, preset the stretch of the stretch receptor

Capsaicin activates a channel that normally functions to detect (what?).

heat

"First pain" and "second pain." What is the axonal difference?

A delta (small, myelinated) vs C (small, unmyelinated

What is the function of the cell that is stimulated by bradykinin?

pain

The head of a neurosurgery patient is opened to expose the brain using only local anesthetic. Answer either: (1) How do they get away with that? Or (2) Why would they do it that way?

no pain receptors in the brain, to make certain they are not messing with a really critical function

There is a cell body in the dorsal root ganglion for touch (not pain) input. Where are the "beginning" and also the synaptic terminals of this cell?

beginning - the receptor itself, end - dorsal column (cuneate and gracile) nuclei

In what way are the functions of the cuneate and gracile nuclei different?

cuneate upper body, gracile lower body

Before it reaches the thalamus, but after it enters the central nervous system, in what way does pain and temperature information from the face differ in its pathway from mechanosensory informationfrom the face?

Strangely, for pain, the pathway first descends (from the pons to the medulla)

The mean two-point discrimination threshold for the fingers is less than 5 for the fingers and more than 45 for the calf. Units?

mm

The VPL of the thalamus connects to the somatosensory cortex. What does VPL stand for?

ventral posterior lateral

The Raphe nucleus and the reticular formation feed to a cell in the dorsal horn in the gray matter of the spinal cord for what purpose?

to modulate pain where it inputs

What does "trp" stand for when applied to channels?

transient receptor potential

A C (nociceptive) fiber synapses in the dorsal horn, and the post-synaptic cell ascends in what part of the spinal cord?

antero-lateral system

In the Brown-Sequard syndrome, where is there reduced sensation of two-point discrimination after a hemisection of the spinal cord?

ipsilateral below lesion

Narcotic analgesics would affect interneurons using what peptide in the substantia gelatinosa of the spinal cord?

endorphin

In contrast to the anterolateral system for somatic pain, where does visceral pain ascend?

in center of dorsal column

What aspect of neural organization explains why the irritation of shingles (Herpes zoster) might be restricted to a small area in the body?

dermatomes

What is the function of bradykinin in sensory reception?

mediator of pain at receptor

A pathway from amygdala and hypothalamus through periaqueductal gray to dorsal horn modulates what sensation?

pain

Discriminative touch for the face comes into the brain by what nerve?

trigeminal (V)

What aspect of Pacinian corpuscle function did Lowenstein demonstrate by peeling off layers of the encapsulation?

it is phasic, i.e. responds transiently

Where does a sensory receptor for discriminative touch make its first synapse?

gracile or cuneate nucleus in lower medulla

Tell me a part of the body where the two point discrimination threshold, measured in mm, is very low. (Pay close attention that "low" refers to mm.)

finger tips

What is it called when you feel a heart attack in your arm?

referred pain

What sensory receptor has inputs via Group I and II afferent axons?

muscle stretch receptor

What is the difference in information carried in gracile vs cuneate tracts in the dorsal columns?

lower vs upper parts of body

Why are the hands and face grossly enlarged in the sensory homunculus?

because of increased somatosensory "magnification" (low two point threshold)

Translate "midline myelotomy is a paliative neurosurgical intervention for cancer patients whose pain is otherwise unmanageable."

for visceral pain, tract is in dorsal columns, and cutting myelinated fibers will decrease suffering in terminal patients

A C nociceptive fiber makes its excitatory connection in the dorsal horn to the cell whose axon is in the contralateral anterolateral system. How does an enkephalin-containing local neuron mediate descending influence?

the interneuron inhibits via a presynaptic connection to the excitatory synapse

Why would a Pacinian corpuscle have a larger receptive field than a Merkel's disk.

being deeper, deformation of a larger skin area would stimulate it

In talking about proprioception, the muscle spindle and the reflex arc, several different myelinated nerve axons were shown. What are the sensory axons called?

IA

Capsaicin gates the VR-1 channel that is normally used for what type of stimulation?

warm

"In summary, the nociceptor is really a chemoreceptor." Name a chemical.

serotonin, prostaglandins, leukotrienes, histamine, substance P, bradykinin

Where (medial vs lateral) do axons from upper body input travel (relative to those from lower body) in the dorsal columns?

Lower limbs are handled medially in gracile tract. Upper limbs are lateral in cuneate tract.

There is somatosensory input from 7 cervical, 12 thoracic, 5 lumbar, and 4 sacral dermatomes. Why doesn't the face input through one of these?

It comes via the trigeminal

"A hemisection of the spinal cord leads to a contralateral loss of spinothalamic input from below the injury." This is in contrast with what other loss of what other system?

ipsilateral of lemniscal

About as much of the sensory homunculus is devoted to the lips as to the legs. Make a statement about two-point discrimination threshold that relates to this point.

lips, tongue fingers have a 1-2 mm two point threshold, legs and back are way bigger

In what way is the periaqueductal gray relevant in the somatosensory system?

part of efferent system to modulate afferent input

***Vision and the brain

A stroke wipes out the connection of the pretectum to the contralateral Edinger-Westphal nucleus but not to the ipsilateral one. How could you infer this with a very simple non-invasive vision test on a cooperative subject?

There would still be a pupillary reflex but not in the contralateral eye

Say something about how the nasal portion of the retina projects to the lateral geniculate nucleus

nasal retina connects to contralateral LGN's layers 1, 4, and 6.

An electrode is in a simple cell that fires action potentials vigorously when stimulated with a thin, vertical stripe of light. How does it respond to a thick stripe in the same location, and why does it react that way?

a lot less or not at all b/c the thick stripe also stimulates the inhibitory surround

Injection into one eye followed by a specialized histological technique demonstrated a zebra-stripe pattern of ocular dominance columns in the visual cortex. Answer either (1) What was injected in the eye? Or (2) What technique was used for the visualization in the cortex?

a radioactive amino acid, audioradiography

You went home and tried what I suggested, shined a flashlight to one eye. Alas, only one pupil constricts. Tell me a place where you have nerve damage.

has to be after the pretectum. maybe between the pretectum and the Edinger-Westphal nucleus (one of two paths) or from there to the ciliary ganglion, to the muscle (on one side)

If Hubel and Wiesel had looked for a grandmother cell instead of the cells they identified (e.g. simple cell), why wouldn't they have gotten a Nobel Prize?

Their systematic approach was very productive, good thing they didn't start looking for a needle in a haystack

How were the ocular dominance columns in normal and visually deprived animals visualized?

audioradiography, histological slices exposed photographic "film"

Occasionally I pointed to how uninteresting the wall was vs the perceptual richness of the map on the wall. Say something about how the receptive field organization in the lateral geniculate nucleus contributes to this difference.

center surround influences contrast

What is the most obvious thing that happens between the pretectum and the Edinger-Westfall nucleus?

goes bilateral

Concerning layers in the lateral geniculate nucleus, answer either (1) What is the main difference between layers 1, 4, & 6 vs 2, 3, & 5? Or (2) What is the main difference between layers 1 & 2 vs 3 to 6?

1,4,6 contralateral, 1, 2 magnocellular

In the "movie" of Hubel and Wiesel's simple cell experiment, how come a wide line of light projected right on target did not elicit firing while a thin line, also accurately aimed, did?

wide hit inhibitory surround also

An oblique electrode track traverses several millimeters of the visual cortex. What change do you notice about the receptive field properties of the firing neurons you encounter?

one eye -> both -> other, (also angle of line)

A radioactive amino acid was injected into one eye. Say one of the several cell biological events that must occur to give an autoradiogram of ocular dominance columns. (I am not asking how to do autoradiography.)

is put into protein, is transported down axon, is transported across synapse, transported down other axon

Why did I tell the story of geese following the Nobel prize winning ethologist Konrad Lorenz in the context of the visual cortex?

sensitive (critical) period

How would you test whether a patient's contralateral connection from the pretectum to the Edinger-Westphal nucleus were disrupted?

light to one eye would not consstrict the contralateral pupil

Specifically, what crossed the LGN (lateral geniculate nucleus) synaptic cleft to allow Hubel to see the ocular dominance columns using autoradiography?

3H labeled protein

Where do the axons of the the temporal retina (nasal visual field) go at the chiasm?

to ipsilateral LGN

What is the word for the special type of "depth perception" mediated by the parallax from focussing both eyes (and neural interactions of binocular cells)?

stereopsis

If a child were born with a congenital cataract in one eye, why should this deserve immediate attention?

brain connections from that eye would vanish without patterened vision

Light stimulation to one eye activates that eye's optic nerve. By what mechanism would there be efferent output to the iris from both occulomotor nerves?

connection to one pretuctum goes bilaterally to Edinger-Westphal nuclei

The inputs from the two eyes to the lateral geniculate nucleus do not mix. In what manner are they kept separate?

they go to different layers, contralateral to 1, 4, & 6, ipsilateral to 2, 3, & 5

A thin bar of light made the simple cell fire quickly. Why did a wider bar not do likewise?

Because the wider bar also hit the inhibitory areas in the receptive field of that cell

What technique did Hubel and Wiesel use to get that picture of the visual cortex with stripes?

Autoradiography, or, inject radioactive amino acid into one eye and observe the protein transported transynaptically from ganglion cell across LGN to cortex

As an electrode is advanced obliquely across columns in the visual cortex, what changes?

One could say preferred eye of input or one could say preferred angle of line

Why did Hubel and Wiesel feed their microelectrode amplifier into a loud speaker?

easy to judge firing rate by the sound

Why did a wide line centered on the simple cell's receptive field elicit less of a response than a narrow line?

even though it stimulates the excitatory receptive field, it also stimulates the surrounding inhibitory ones

While an electrode is advanced obliquely through the cat's visual cortex, first the left eye predominates, then the right eye. What else has been changing during that advancement?

preferred angle

When is the critical (sensitive) period for development of binocular connections in the cat visual cortex?

birth to 2 & 1/2 mo

When autoradiography was used to demonstrate ocular dominance columns, how did the film (photographic emulsion) get exposed?

radioactivity (in cortex protein) exposed film in the dark



***Neural Development

In contrast with signalling via the heterotrimeric G protein, signalling by Wnt, FGF, BMP, shh and RA were posited as going in a fairly direct pathway into the nucleus. Say something about the effect these ligands have in the nucleus.

ultimately they control transcription into mRNA of specific genes

"Inside the larva are these pieces of tissue that are determined to become adult structures but are not yet differentiated. Say something about them (e.g., What are they called? When do they differentiate?).

imaginal disks have cell proliferation in larvae then they differentiate into adult structures in the pupa case

The genes involved in homeotic mutants-- answer either (1) What shape is the critical domain of the protein they encode? or (2) What is the function of that protein?

helix turn helix, bind DNA to activate transcription

Sevenless is a receptor tyrosine kinase. Name another protein in the sevenless signal transduction pathway.

boss, downstream of receptor kinase, sos, ras, MAP kinase,

There are 3 layers (suffix ...derm). From which is the neural plate derived?

ectoderm

Give one of the fates of neural crest.

sensory ganglia, autonomic ganglia, adrenal medulla, non-neural cells like melanocytes

In a classic example of induction, what does an out-pocketing of the diencephalon make the overlying ectoderm turn into?

lens and cornea of the eye

Your lab is the best in the world in all histological techniques including the Golgi technique. And yet, NSF and NIH resoundingly reject your grant proposal to look for differences in growth cones in the hypothalamus in male vs female rats at the age when males continue to get heavier but females do not. What is the reviewers' criticism?

there is no axon pathfinding in the adult mammalian brain

"The chick spinal cord generates an excess of neurons prior to the differentiation and innervation of the limb. Normally some of these neurons are lost..." Answer either (1) What is the evidence for the first statement? or (2) Say something about this process of loss of neurons.

more neurons if supernumerary limb bud, less if ablated limb bud; apoptosis

A cell from the mouse inner cell mass is treated for 4 days with retinoic acid after 4 days without retinoic acid. This protocol converted the cell from what kind of cell to what kind of cell?

from an embryonic stem cell to a neuronal precursor

Why are the first genes to guide Drosophila embryology referred to as "maternal genes?"

the mRNA is active in, and the protein laid down by, the mother, not the zygote

Say something about the receptor in the MAP kinase (or the sevenless) signaling pathway.

transmenbrane receptor tyrosine kinase

Somehow a cell is told to become R7 in every ommatidium (facet) of the Drosophila compound eye. Answer either (1) What cell tells that cell to become R7? Or (2) What is the ligand on that cell that sends the signal?

R8, boss

For retinoic acid, [answer either] (1) What would happen if you treated embryonic stem cells with retinoic acid? Or (2) What would be required for it to activate transcription of specific genes?

they would become neural stem cells, a retinoic acid receptor (RAR), and response element (RARE) and dimerization with another hormone-receptor complex

In "diseases in a dish," how did S. S. Hall propose to get motor neurons from an elderly donor, one from a family with familial ALS, to test drugs on?

skin cells would be used to get neurons and only then would they begin

Why did they decide to call bicoid a "maternal gene?"

mRNA expressed in maternal cells where protein is made (and put into egg)

If you tried Sperry's experiment, turning the eye up-side-down and letting it reconnect to the tectum, before stage 28, how would the frog respond to a moving fly presented to the side of its visual field?

it would flick its tongue to the correct place

Dogma has it that there is no regeneration of neurons in the mammalian central nervous system. Describe how post-mitotic cells exit from the cell cycle.

arrest in G1

What does the neural crest become?

sensory neurons, sympathetic nervous system, adrenal medulla, melanocytes

What finding led to the conclusion that apoptosis reduced the number of spinal motor neurons to the right number to innervate a limb?

there were enough precursors of cells to innervate two limb buds

In all of our coverage of neuroanatomy of the spinal cord, with terms like "ventral horn" and "dorsal columns," there was no mention of floor plate and pMN. Why not?

these are in the embryonic neural tube

What kind of a molecule is a chemokine receptor?

g protein coupled

"Olig-2 is expressed in oligodendrocyte precursors and it is a basic helix-loop-helix factor." What does such a factor do in the cell?

regulate transcription

What is the difference at birth vs. at maturity of how many spinal motor neurons can innervate one end plate?

at maturity, only one, more earlier

In the time since the stem cell debate was in the forefront the federal administrative scrutiny, what advancements have lessened the ethical dilemma?
 
there are sources of stem cells other than embryonic
 
In what fundamental way are bicoid and kruppel different in the locations where their genes act?
 
bicoid mother ("maternal"), kruppel embryo ("zygotic")
 
Say something about the comparison of ras with a heterotrimeric G protein.
 
ras is a G protein, smaller, monomeric
 
Several signaling ligands were introduced to you: retinoic acid, wingless, fibroblast growth factor, bone morphogenetic factor and sonic hedgehog. Which pathway most closely approximates the one initiated by bride of sevenless and why?
 
fgf b/c it is membrane receptor tyrosine kinase signaling through ras and MAPK
 
In between ectoderm and the neural groove are cells whose fate is very different from those of the neural groove. In what way?
 
neural crest will become components of peripheral n.s.
 
Here is a list of cell types: sensory neuron, melanocyte, adrenergic sympathetic neuron, cholinergic sympathetic neuron, and chromaffin cell. Answer either: (1) What is the common ancestor? Or (2) How is it that they assumed different fates?
 
neural crest progenitor, "growth factors" (NGF, LIF, glucocorticoids, etc.)
 
Embryologists tell us that the retina and optic >nerve< are part of the central nervous system. So you were told earlier. Now add some details that justify that position.
 
optic vesicle becomes optic cup, outpocket from diencephalon
 
Sperry proposed neurobiotaxis for how each optic nerve found the right address in the tectum. What had been the previous thinking?
 
weiss, resonance, connection from eye assigned function of central cell
 
Several times, the neuromuscular junction was used as a model system in development and "learning." Where did agrin fit into the discussion?
 
agrin mediates the localization of acetylcholine receptors to the end plate
 
In a comparison of spinal motor neurons on the normal side vs the side where a second limb bud had been transplanted, how does apoptosis apply?
 
there would be zillions of spinal motor neurons, decreased by apoptosis on the basis of limited target
 
Describe the geometry of the TrkA receptor for nerve growth factor.
 
it is a single membrane passing enzyme that dimerizes on binding the ligand
 
Receptor molecules on the axonal growth cone are inhibited by well-studied molecules derived from damage to (what?) in CNS injury.

oligodendrocytes

"Alpha and gamma secretases act on p75ntr to yield an ECD and an ICD." Translate.

these enzymes cut in the membrane neighborhood to give intracellular and extracellular domains

Fibroblast growth factor (FGF) is the ligand in a pathway with ras and MAPK signaling to the nucleus. Describe the receptor, pick one (1) location (in the cell), (2) structure, or (3) specific biochemical function.

1 membrane, passes one time, dimerizes, phosphorylates tyrosine

A mouse embryonic stem cell can be converted to a neural stem cell that expresses neuron-specific proteins by what important developmental ligand?

retinoic acid

With respect to anterior vs posterior (as opposed to segmentation), why is bicoid referred to as "maternal" (as opposed to zygotic)?

laid down into egg by mother as opposed as involving expression after the egg is fertilized

"Bride of sevenless (Boss) is the ligand for sevenless (sev). Answer either: (1) What cell's expression of Boss "tells" the R7 precursor to become R7? Or (2) What happens to this precursor if sev is mutant?

1 R8, 2 becomes cone cell

A sympathetic progenitor can become an adrenergic neuron or a cholinergic neuron." How is this determined?

with NGF vs CNTF

An explant of developing spinal cord is placed near some tissue that is a source of netrin. What is observed?

neurites going toward source

In the cerebellum, what cell type is "inside" the Purkinje nuclear layer? (Its terminals are "outside" [i.e. toward the meninges] the Purkinje nuclear layer.)

granule cell

"In the neural tube, cells exit the cell cycle to become post-mitotic neuroblasts." Address either (1) At what stage are they arrested in the cell cycle? Or (2) At what surface are these new cells found?

G1, pialRemoving or adding a supernumerary limb bud speaks to a general mechanism to regulate the number of spinal motor neurons. How is this number regulated?

too many precursors, apoptosis prunes numbers

Ligands such as shh, RA, FGF, BMP and Wnt eventually control transcrption. Nane one receptor corresponding to any of these ligands.

patched, retinoic acid binding protein, receptor tyrosine kinase, receptor serine kinase, frixxled

R8 tells a cell to become R7. Name one famous protein in this cascade.

boss, sev, sos, ras, MAPK, (others)

What is the precursor of sensory ganglia, autonomic ganglia, adrenal medulla or melanocytes (depending on which factors are acting)?

neural crest

The optic vesicle, an outpocket of the diencephalon, eventually forms the retina. What do these induce the overlying ectoderm to form?

lens and anterior portion of eye

"The S stage occurs near the pial surface." Translate.

synthesis of DNA in the cell cycle (between mitoses) is when nuclei are on the outer part of the neural tube

In Weaver mutant mice, granule cells are missing, but it is the fault of what other cell type?

(Bergman) glia

Rotating the frog eye up-side-down gives opposite results if done in the adult vs. a few days before Harrison stage 28. What is the behavior in the adult after early rotation?

animal will flick its tongue (to catch an insect) in the correct direction

Filopodia protrude from what important structural specialization in axon path finding?

growth cone

What are integrins and cadherins used for in nervous system development?

contact guidance

What was changed in the adult spinal cord if a limb bud had been ablated earlier?

number of spinal motor neurons for that limb is lower

What is apoptosis and why is it so important in development?

programmed cell death. If too many cells are made, extras must be eliminated.

"Cytokines include trophic factors, hematopoietic factors and growth factors." In which category is NGF?

Despite ist name (nerve growth factor), it is a trophic factor.

The patched receptor acts in concert with the smoothened protein to mediate the response to what famous developmental ligand?

shh

Larvae of holometabolous insects have tissues determined to become adult structures. What are these called?

imaginal disks

Name something that neural crest gives rise to.

sensory ganglia, autonomic ganglia, adrenal, melanocytes

What process is agrin involved in in muscle cell development?

aggregation of ACh receptors

In the sevenless signal transduction cascade, what is the name of the small GTP binding protein?

ras

Contradicting Weiss's resonance principle, how did Sperry explain proper connection of ganglion cells to tectum?

neurobiotaxis directs axon tips to correct places in tectum

Why is bicoid referred to as a maternal gene?

the mRNA is transcribed in mother

What is the output neuron of the cerebellar cortex?

Purkinje

On what kind of a molecule would you find a domain such as a homeodomain?

protein

An antibody to nerve growth factor (NGF) causes what part of the nervous system to be lost?

sympathetic n.s.

In axon path-finding, what is the bulbous knob with extensions at the tip?

growth cone

Name a neurotrophin that uses the Trk ("track") receptor.

NGF (and others)

Shh and Wnt are two important secreted ligands used in developmental signalling. Tell me the receptor (for one of them).

patched frizzled

The word "pluripotent" is used in reference to what type of cell?

embryonic stem cells, neural precursors

How does Sperry's notion of "neurobiotaxis" explain the poor visual performance of a frog whose eye has been inverted?

upside down eyes axons grew to addresses in tectum as if the eye did not know it was upside down

The optic vesicle is an outpocket from the diencephalon. What does the optic vesicle induce in the overlying ectoderm?

lens

The structure that will eventually fold in to make the neural tube is called the neural plate. From what major embryonic layer is the neural plate partitioned?

ectoderm

What is it that gives rise to sensory and autonomic ganglia, adrenal neurosecretory precursors and melanocytes?

neural crest

"Receptor tyrosine kinase." What does that mean? Give an example in developmental signalling.

it is a membrane receptor protein with enzymatic activity to phosphorylate itself on tyrosine residues, sevenless

A sympathetic progenitor can either become cholinergic or adrenergic. What determines which pathway?

NGF vs CNTF

What is the difference in distribution of the nicotinic acetylcholine receptor in a muscle cell before vs. after a neuromuscular junction is formed?

before distributed, after under junction

What effect does transplantation of a supernumerary limb bud in the chick embryo have on spinal motor neurons?

extra ones formed

What is the difference in appearance of an explanted dorsal root ganglion with vs. without NGF in the medium?

with has neurites growing out

Ligands such as shh, RA, FGF, BMP and Wnt eventually control transcrption. Nane one receptor corresponding to any of these ligands.

patched, retinoic acid binding protein, receptor tyrosine kinase, receptor serine kinase, frixxled

R8 tells a cell to become R7. Name one famous protein in this cascade.

boss, sev, sos, ras, MAPK, (others)

What is the precursor of sensory ganglia, autonomic ganglia, adrenal medulla or melanocytes (depending on which factors are acting)?

neural crest

The optic vesicle, an outpocket of the diencephalon, eventually forms the retina. What do these induce the overlying ectoderm to form?

lens and anterior portion of eye

"The S stage occurs near the pial surface." Translate.

synthesis of DNA in the cell cycle (between mitoses) is when nuclei are on the outer part of the neural tube

In Weaver mutant mice, granule cells are missing, but it is the fault of what other cell type?

(Bergman) glia

Rotating the frog eye up-side-down gives opposite results if done in the adult vs. a few days before Harrison stage 28. What is the behavior in the adult after early rotation?

animal will flick its tongue (to catch an insect) in the correct direction

Filopodia protrude from what important structural specialization in axon path finding?

growth cone

What are integrins and cadherins used for in nervous system development?

contact guidance

What was changed in the adult spinal cord if a limb bud had been ablated earlier?

number of spinal motor neurons for that limb is lower

What is apoptosis and why is it so important in development?

programmed cell death. If too many cells are made, extras must be eliminated.

"Cytokines include trophic factors, hematopoietic factors and growth factors." In which category is NGF?

Despite ist name (nerve growth factor), it is a trophic factor.

***Memory at the cellular level


Learning with electrical stimulation of the brain -- Say something about the more traditional situation for this kind of learning (e.g. what that kind of learning is called, the nature of the behavior, example reinforcements).

operant condition, bar press, water or food if water- or food-deprived

You are studying habituation as a model of learning. Convince us that the phenomenon is habituation instead of sensory adaptation or muscle fatigue.

you would need to show that it is a change in a synapse, like change of EPSP strength

The fruit fly Drosophila is given electrical shock repeatedly in the presence of a specific odor, and it learns to avoid the area where that odor is present. Eventually, it was found that the cAMP signal transduction pathway was important in this learning. What strategy allowed them to make this conclusion?

obtain mutants with learning defects

"After a train of stimuli to axons of CA3 pyramidal axons (Schaffer collaterals) the response of the postsynaptic cell (CA1 pyramidal neuron) is larger." Answer either (1) What is this simple kind of learning called? or (2) What part of the brain was being studied?

long term (lasting) potentiation, hippocampus

If excitation of the climbing fiber and the parallel fiber are paired, there is a decrease in the effectiveness of the glutaminergic AMPA receptor. Answer either (1) What is the postsynaptic cell? or (2) What is this simple model of learning called?

purkinje cell, long term depression

What is the modification of PKA that characterizes the difference between short term sensitization and long term sensitization?

ubiquitin hydrolase breaks down regulatory (inhibitory) subunits, making the activation persistent.

What is the difference at birth vs. at maturity of how many spinal motor neurons can innervate one end plate?

at maturity, only one, more earlier

Long-term-potentiation is a synaptic model for learning. What is the analogous model for change in efficiency of transmission at the neuromuscular junction?

post-tetanic potentiation

"Pairing parallel and climbing fiber activations cause AMPA receptors to be internalized (from the post-synaptic membrane into intracellular vesicles)." Answer either (1) On what cell? Or (2) What is this model of learning called?

Purkinje cell, long term depression

"Potentiating GABA inhibition with diazepam widens columns." Why was this statement offered in the context of cellular bases of learning?

applies to the (re) establishment of ocular dominance columns

After half an hour in a dark room, you are much more sensitive. After a prolonged forceful muscle contraction, that contraction becomes weaker. Why is Kandel's work on habituation of the gill withdrawal reflex considered a model of learning while the other two examples are not?

at a synapse, not receptor adaptation or motor fatigue

How was ubiquitin hydrolase shown to be relevant in long-term sensitization?

breaking down inhibitory subunits activates PKA long term

Using Diazepam, how was GABA implicated in visual experience and cortical connectivity?

GABA-A receptors needed for developmental maintenance in visual experience, diazepam blocks

"Habituation of the gill withdrawal reflex in Aplysia:" What aspect of this work shows that it is not receptor adaptation or muscle fatigue?

it is at a synapse, not receptor or muscle

Classical (Pavlovian) and operant conditioning are referred to as "associative learning." What are the properties of the performance of a rat in a Skinner box that qualify it as "associative learning?"

repeated pairings of reinforcement with bar press

With the help of the ubiquitin system, how is long term sensitization achieved via PKA?

the inhibitory subunits are gone long term

A Schaffer collateral is stimulated to "tetanus" to show long term potentiation at the synapse with a CA1 pyramidal neuron. What is the control for this experiment?

another collateral is not prestimulated but it is tested (and shows no LTP)

"Hold that thought." How did Donald Hebb propose that was achieved in the 1940s?
 
reverberating circuits of neurons with excitatory connections with each other
 
Why would a congenital cataract in one eye need to be treated quickly?
 
Appropriate development/maintenance of binocularly innervated cells in the visual cortex requires patterned vision from both eyes
 
Food can be repeatedly paired in classical and instrumental conditioning. How does the presentation of food differ in these two models of associative learning?
 
Classical, food is unconditioned stimulus paired with conditioning stimulus (bell), instrumental (operant) food is positive reinforcing stimulus paired with behavior (bar press)
 
Why is habituation of the gill withdrawal considered to be a simple model of learning instead of sensory adaptation or muscle fatigue?
 
It is change in synapse, not sensory receptor or muscle
 
In the difference between the shortest term "learning" and long term sensitization in Aplysia, why was ubiquitin hydrolase found to be useful?
 
Mediates longer term activation of PKA by targeting the inhibitory subunits for degradation
 
In a study of long term potentiation, a Schaffer collateral is stimulated repeatedly while recording from a CA1 pyramidal cell. Answer either (1) What changes? Or (2) What is the control?
 
The response of the CA1 cell gets bigger, but not for stimulation of another collatoral that had not been repeatedly stimulated
 
In a study of long term depression in Purkinje cells, how is the sensitivity of AMPA receptors decreased?
 
Receptors got internalized (pulled from membrane)

Even though it has been over 50 years since his famous textbook, Donald Hebb is still mentioned frequently in neuroscience. In what context?

reverberating circuits of excitation for short term memory

How does transcription of ubiquitin hydrolase promote long term sensitization?

breaks down regulatory (inhibitory) subunits of PKA

Why has the brain slice technique proved useful in studies of long term potentiation in the hippocampus?

enough neural circuitry remains, yet neurons can be reached by electrodes

In addition to Na+, what ion is expecially important in the signal transduction cascade from the NMDA receptor to long term potentiation?

Ca2+

What is the output neuron of the cerebellar cortex?

Purkinje

Habituation of the gill withdrawal reflex was used by the Nobel Prize winner, Kandel, as a model of learning in what organism?

Aplysia

One question implied that the NMDA receptor is a channel. The AMPA receptor is invoked in addition to the NMDA receptor in long-term potentiation and depression.
What kind of a receptor is the AMPA receptor, and to what transmitter does it respond? (2 points)

channel, glutamate

Drosophila were shocked each time they went toward a particular odor, and mutants like dunce did poorly. What kind of learning is this?

operant

To what kind of molecule does CREB (cAMP response element binding transcription factor) bind (other than cAMP, of course)?

DNA

A difference between short- vs. long-term sensitization was the breakdown of PKA's regulatory subunit. How would this change the duration of the cellular effects?

regulatory is inhibitory so catalytic stays activated

Suturing a cat's eye closed alters the occular dominance columns. How can this be when light can still pass through the eyelids?

it deprives of patterned input

Adaptation and fatigue are decreases in responsivity at sensory and muscle levels. An analogous decrease, mediated at the synaptic level, is considered a simple type of learning. What is this called?

habituation

"EPSPs are bigger in CA1 pyramidal cells after stimulation to Schaffer collaterals." What simple type of learning is this, and in what location in the brain?

LTP long term (lasting) potentiation, hippocamus

"In summary, a cellular explanation of learning involves changes in synaptic signal transduction." Give an example from Drosophila.

dunce - phosphodiesterase, rutabaga - adenylyl cyclase, amnesiac - peptide transmitter that stimulates adenylyl cyclase

Internalization of AMPA receptors weakens the Purkinje cell's response at the parallel fiber synapse. What simple type of learning is this, and in what location in the brain?

LTD long term depression, cerebellum

What happens between birth and maturity that makes the wiring of motor neurons to striated muscle cells a model of plasticity?

muscle end plate may have more than one motor neruon connected at first, only one later

What model of learning is "a diminution in the response after repeated stimulus administrations not attributable to sensory adaptation or motor fatigue?"

habituation

By what molecular mechanism would breaking down a PKA regulatory subunit cause long term sensitization?

the catalytic subunits would be activated long term

Drosophila are shocked repeatedly in the presence of a particular odor, then they avoid that odor. What kind of learning is that?

beyond habituation and sensitization, this is associative learning (operant (instrumental) conditioning)

***Language and Cognition

Patients with damage to what brain area have difficulty with the line bisection task?

parietal, temporal, frontal, superior occipitofrontal fasciculus

Which of the 6 cortical layers receives input from the thalamus?

iv

Motor aphasia (difficulty speaking but normal speech recognition) is associated with lesions in what area?

broca's

What is the evidence that language is localized on the left side of the brain even in left-handed people?

wada procedure, anesthetize one side of the brain by injection into one carotid

With careful eye fixation, images of objects could be presented to one side of the brain of Roger Sperry's subjects. With the same optical presentation, both hemispheres of a normal subject "know" what was presented. How?

information crosses corpus callosum

Describe the performance on the line bisection task in a patient with hemispatial (contralateral) neglect syndrome.

nowhere the middle

Language is on the left side of the brain even in left-handed people." How was this shown?

wada procedure, put anesthetic (sodium amytal in one carotid

What do you do to present a visual stimulus to only the left cerebral cortex in a patient whose corpus callosum has been severed?

right visual field (keep eye fixation) crosses (for both eyes) since optic chiasm is not severed

What do you call fibers that connect adjacent gyri?

arcuate

An old term, still used, for all the cerebral cortex excepting the primary sensory and motor areas.
 
association cortex
 
Draw how a contralateral neglect syndrome patient behaves on a >bisect the line< task.
 
a big horizontal line will not be divided in the middle, but way to one side
 
How come you can show something to someone with a severed corpus callosum severed and have that information go to only one hemisphere?
 
if they fixate on one side of the stimulus, image goes to one temporal retinal field and the other nasal retinal field that project ipsilateral to the temporal retinal presentation
 
Recent literature, "parietal-frontal pathway subserving spatial awareness" and "widespread cortical networks underlie memory and attention" (2005) showed neurosurgeons addressing what bizarre human syndrome?

contralateral (hemispatial) neglect

FOXP2's function in zebra finches and rodents relates to what behavior in humans?

speech

How can one side of the brain be anesthetized to study laterality of language ?

circle of Willis notwithstanding, barbituate to one intenal carotid goes preferentially to one side of the brain

A subject stares at a fixation point in front of his or her nose. An object to the right of the fixation point is displayed. Say why the subject can (or cannot) say what is seen.

right visual field = left retinal field, goes to left hemisphere the side with language

In testing a split-brain subject (with a severed corpus callosum), how can you show a visual stimulus to only one hemisphere?

present to temporal retina that innervates ipsilaterall;y (with eye fixation)

Washoe, Sarah and Nim Chimsky were all used in a study of what capability?

language in chimps

What is the more common name applied to the "archicortex" folded in between the neocortex and the paleocortex?

hippocampus

Hemispatial (contralateral neglect was found to result in damage to what brain area (or the white matter under that surface feature)?

parietal lobe

In a subject with a severed corpus callosum, can the right hemisphere "know" what stimulus was presented to it?

yes but it cannot say

How could administering sodium amytal to the carotid address the question of the unilateral location of speech?

into one carotid anesthetizes one side of the brain

How is performance on the line bisection task diagnostic of neglect syndrome?

easy to see if patient cannot decide where the middle of a line is, even during brain surgery

In studies of speech localization to Broca's area, how did Sperry present a visual stimulus to only the left hemisphere?

Right visual field goes to left temporal retina and right nasal retina (to left brain)

***Biorhythms

Pontine to (what?) to Occipital, these are "spikes that jerk you at the onset of sleeping.

geniculate

"During arousal, there is alpha blocking." Answer either (1) What is alpha? or (2) How would you observe alpha?

relaxed EEG with eyes closed 8-13 Hz, record EEG with electrodes on the scalp.

A sleep pathway involving serotonin and norepinephrine in the area between the pontine reticular formation and the midbrain goes to spinal motor neurons to mediate atonia with what neurotransmitter?

glycine

Why do they call REM sleep "paradoxical sleep?"

the EEG has the aroused pattern (alpha blocking)

Explain in terms of Ashoff''s rule how the human free-running circadian rhythm deviates from 24 hours.

it is longer than 24 hours when a diurnal animal is in the dark, it is like the person is waiting for dawn

For mice OR for Drosophila, state the name of a visual pigment molecule involved in entrainment that is not rhodopsin.

melanopsin, cryptochrome

The discoveries of long (29 hr) and short (19 hr) per (period) mutants paved the way to the characterization of how the PER gene and the protein it encodes function in the non-mutant animal. How does PER contribute to the biological clock?

the PER mRNA and protein increase and decrease on a daily cycle

Why is REM sleep called paradoxical sleep?

eeg resembles that of the aroused state

"It is like a sympathetic ganglion in the brain." Answer either (1) Why? Or (2) What structure?

puts out norepinephrine, locus coeruleus

What place in the brain has photoreceptors that are important in entraining circadian rhythms in vertebrates with small heads?

pineal

Say something about the location or function of melanopsin.

in ganglion cells, can mediate entrainment to light/dark cycle even if there are no rods

Explain why most people want to stay up late and get up late in terms of a "rule" proposed by a famous circadian biologist.
 
human (diurnal animal) circadian rhythm is longer than 24 hours according to Ashoffs rule
 
In a neurochemical circuit initiated by the serotonin and norepinephrine secreting parts of the brain, motor neurons are inhibited during sleep with what spinal cord inhibitory transmitter?
 
glycine
 
Say something (anything) about melanopsin, What animals have it? What cells have it? Why is it called "melanopsin?"
 
frogs have it in skin mediating melanin dispersal, in ganglion cells of mammals to mediate entrainment

 How would you know if a subject is in stage I, II, III, or IV sleep?
 
on the basis of EEG, slow waves for deep sleep
 
For REM sleep, what happens to the electroencephalogram (EEG)?
 
becomes like EEG of awake, aroused subject

Why would a cat restrained with a dish of water in front of it be specifically deprived of REM sleep?

loss of neck tone during REM would drop face in water and wake the cat up

Why is REM sleep called paradoxical sleep?

EEG appears like aroused state

A person put in the constant darkness after having been in a light-dark cycle of 12 hr on - 12 hr off will have an activity cycle that is not exactly 24 hr. Give details.

would go to >24 hrs, sleep in on Saturday morning

By what visual pigment do ganglion cells of the eye mediate entrainment of a circadian rhythm?

melanopsin

"Carotenoid deprivation decreases visual sensitivity in Drosophila (obviously) but not the sensitivity to stimuli to change the cycle for pupal emergence." What does that mean about the photoreceptive pigment?

it is not a rhodopsin based on retinoids (it is cryptochrome)

"Per mutations affect the ultradian rhythm of the courtship rhythm in the same way they affect the circadian rhythm." What does ultradian mean in this context?

way shorter than 24 hrs, courtship song is

During paradoxical sleep, what inhibitory transmitter goes down to spinal motor neurons?

glycine

Relate the conventional wisdom that most people would like to stay up later and stay asleep when the alarm goes off to the expression "circadian rhythm."

about a day is a little longer than 24 hrs for most people

In which cells does melanopsin reside to mediate photic entrainment in mammals?

ganglion cells

EEG spikes from pontine reticular formation to geniculate to occipital cortex (PGO spikes) are associated with the onset of what?

REM sleep

What is cryptochrome used for?

blue light receptor interacts with other proteins for circadian rhythm

What part of the brain spreads norepinephrine to a wide brain distribution?

locus coeruleus

When are there slow (delta) waves in the EEG?

deep (non REM)

What happens with the levels of the protein product of the period gene in Drosophila?

it cycles

In an experimental animal, what does the researcher change to go from entrainment to free-run?

the lighting cycle (to constant light or dark)

Why is REM (rapid eye movement) sleep called "paradoxical" sleep?

EEG as if awake (and respiration and circulation higher)

"A person's endogenous circadian rhythm has a period of >24 hours." What would you do to demonstrate that?

after entraining on a 24 hr photoperiod, go to constant lighting (free run) and watch it go to over 24 hr

Very recent literature demonstrated that mice lacking rod and cone photoreceptors are blind but they still could be entrained to a photoperiod. What is the photoreceptor (pigment and cell type)?

melanopsin ganglion cells

Sleep disorders and their treatments were put into the context of excitatory vs inhibitory transmitters. Serotonin was depicted as excitatory. What transmitter, derived from serotonin, was in the inhibitory category?

melatonin

"PGO spikes are seen at the onset of REM." Translate.

PGO (pontine reticular formation-geniculate-cortex) spikes are seen in the EEG at the beginning of rapid eye movement sleep

What is the transmitter of the locus coeruleus?

NE

Why do they call them "circadian" rhythms?

about (not exactly) a day for endogenous biological rhythms

In lizards, light stimulates the pineal. In humans, light affects the pineal. How?

from eye to hypothalamus by circuitous route to pineal

Cryptochrome is one interesting pigment and circadian receptor. Name another (other than rod and cone rhodopsins).

melanopsin

"PER is a nuclear protein whose mRNA and protein cycle." Translate.

the way circadian genes work in circadian timing is that the protein feeds back to regulate its mRNA (which of course makes the protein) hence levels go up and down

***Emotion



Say something about where the brain was severed in the classic Bard experiments addressed to the presence or absence of "sham" rage.

if a hypothalamus that is deprived of cortical connection is still able to feed down to the reticular formation, there is sham rage

"The 'pyramidal smile' (voluntary facial paresis) results from an inability to voluntarily move the lower facial muscles on one side due to a unilateral lesion. Answer either how you could over-ride this distorted smile or what the symmetrical smile is called.

in the involuntary response, say, to humor, one gets the Duchenne smile

How do you prepare an animal to demonstrate that electrical self stimulation can serve as a positive reinforcement?

anesthetize, install electrodes with head mount, allow recovery, plug in

Duchenne noted that people with certain kinds of brain damage could not "will" a symmetrical smile. How could you elicit a symmetrical smile from such people (without resorting to "faradizations")?

elicit a spontaneous smile (emotional, tell a joke)

"The limbic system has been implicated in olfaction, emotion and memory - whew!" Which part was involved in classic studies of long term potentiation directed toward understanding memory?

hippocampus

A graduate of a neuroscience course is required to be able to say who Phineas Gage was.

a guy who had a spike blown through his brain and acted strangely after that

Patient SM has Urbach-Wiethe syndrome that caused bilateral destruction of the amygdala. In terms of recognition and drawing of facial expressions, what was her specific and unusual deficit?
 
could not draw or recognize fear

What is the main motor nerve to control facial expression?

facial (7)

Why would paralysis be a more likely consequence of stroke in the lower portion of the face than in the upper portion?

upper is bilaterally innervated, lower is not

Lesions to the lateral hypothalamus resulted in a thin rat, and so the lateral hypothalamus was referred to as a hunger center. An alternative interpretion involved the disruption of
what system involved in affect and motivation?

interrupt dopaminergic motivational tract

What part of the cerebral cortex is in the limbic system?

cingulate

Dopamine comes to the caudate from what brain structure?

substantia nigra

With brain cuts in and around the hypothalamus and with stimulations of the hypothalamus, Bard and (the Nobel prize-winning) Hess (respectively) studied what process?

rage (emotion)

Under what circumstances would a rat give itself electrical stimulation of the brain?

electrode in hypothalamus, stimulation is reinforcement (reward), will press bar in Skinner box

In voluntary facial paresis, a person with unilateral damage to fibers from the motor cortes, the smile will be crooked. Under what circumstances will the same person give a symmetrical smile?

a spontaneous smile resulting from humor

What happens to a monkey with a lesion in the amygdala?

get less aggressive, hypersexual

Why is it an oversimplification to call the lateral hypothalamus a hunger center on the basis of lesion experiments?

there are logical problems, also the medial forebrain bundle traverses the LH, and it has many controls on motivation

In the many functions attributed to the limbic system, what function did Kluver & Bucy attribute to the amygdala?

mood on a scale from cuddly to ferocious

***Neuroendocrinology

There are many differences in brain organization of young male vs female people and rats, feeding behavior (body weight) being one example. How AND when are these differences organized?
 
there is perinatal testosterone in males (there is virtually none in children or prepubertal juveniles)
 
In the John-Joan-John (Bruce-Brenda-Dave) story, Money's theory about gender identity led to the follow-up treatment from the circumcision. What was Money's proposal?
 
that gender identity was determined more by environmental factors than by chromosomal or early hormonal factors

In Drosophila, the number of X chromosomes determines gender (XX being female, one X being male). Say something about how this situation is the same or different for humans.
 
a gene on the Y leads to development of testes which make testosterone and Mullerian inhibiting factor
 
Where, according to Simon LeVay's data, do homosexual vs heterosexual men have differences in their brains?
 
interstitial nucleus of the anterior hypothalamus

Testosterone under the skin of a female rat pup would do what to the feeding behavior when she is an adult?

feeding would be more like that of a male, animal would get heavier than a female

Part of the pituitary releases peptides, including ADH (antidiuretic hormone = ADH) that are made in the hypothalamus, and so this part of the pituitary gland is really an extension of the brain rather than a real endocrine gland. Answer either (1) What is this part of the pituitary called? Or (2) What is the other peptide hormone released from this part of the pituitary called?

posterior pituitary (neurohypophisis), oxytocin

What does the story about the sex change operation of a young twin after a mishap in the circumcision operation tell us about gender identity?

it is not based on upbringing as much as previously thought, more biology

Under what circumstances would the adrenal cortex lead to alterations in gender identity or sexual morphology?

congenital adrenal hyperplasia would tend to masculinize female morphology and behavior

How in the world did your professor get from testes at twelve to androgenic alopecia?

testes at 12 is from genetic lack of 5 alpha reductase which creates di hydro testosterone that contributes to the sex-limited trait of baldness

What differences did Simon LeVay find among men in the interstitial nucleus of the anterior hypothalamus?

homosexual vs heterosexual men differ, the homosexual males have a higher cell count and volume, resembling those of women

How is the somatosensory cortex different for non-lactating vs lactating female rats?

there is a larger representation for the ventrum (where the nipples are) if lactation

Say why Money was (or was not) correct about environment dominating over biology in determining gender identity.

the chromosal boy turned to a girl was never adjusted to being a girl, so biology > upbringing in contradiction to Money's idea

What is the product of 5-alpha-reductase?

dihydrotestosterone (DHT)

Name at least one of the substances in early male development contributing to sexual dimorphism.

testicular determining factor, testosterone, Mullerian Inhibiting Factor

Why was the term "receptive fields" applied to describing the difference between lactating and non-lactating rats?

size of receptive field changes with the increased sensory inptu from ventrum (nipples)Where does estradiol bind in the brain?
 
All over, but strongly in hypothalamus
 
Human metabolism creates cholesterol. Insect cant do this. Why would cholesterol be an essential nutrient if the body could not biosynthesize it?
 
Precursor of steroid hormones
 
Why would hyperplasia of the adrenal cortex lead to masculinization of a female?
 
Adrenal cortex makes androgens that act like testosterone
 
The Mullerian ducts degenerate and the Wolffian ducts are supported. Answer either (1) What could lead to this? Or (2) What is the result?
 
Wolffian ducts become epididymus, seminal vesicles etc, sexual differentiation of male
 
In his studies of the interstitial nucleus of the anterior hypothalamus (INAH), why did Simon LeVay feel the need to include a control group of heterosexuals who had died of AIDS?
 
Because most of his male homosexual subjects had died of AIDS
What changes, and in whom, in congenital adrenal hyperplasia?

females may be masculinized (anatomically and behaviorally)

Simon LeVay presented evidence that waht sexually dimorphic area of the brain was altered in homosexual males?

part of hypothalamus

Why would there be a different number of motor neurons in males vs. females in Onuf's nucleus of the spinal cord controlling the perineal muscles?

to mediate male specific behavior

Adult male rats are heavier than females. What is the schedule of testosterone administration to effect a change toward male weight in the female?

one neonatal application

Money's attempt to demonstrate that upbringing predominated over chromosomal makeup in gender identity backfired. How?

boy surgically changed to girl was never adjusted

A figure was shown demonstrating estradiol binding in many parts of the brain, especially the hypothalamus. Where, in the affected brain neurons, would you expect most of this binding to occur?

bound to intracellular receptor protein to control gene trancription

How does the somatosensory projection change during lactation?

larger area and smaller receptive fields for ventrum of dam

***Memory

Hippocampal lesions interfered with performance on the radial 8 arm maze. Why was the memory this task tapped into called >working memory?<
 
if rat can scurry to all 8 arms without repeating one, it must remember a map short term
 
What does learning a mirror-drawing task say about Brenda Milners famous patient HM who had bilateral hippocampal lesions?
 
non-declarative task while declarative memory is lost
 
Rationalize why I was so dogmatic to say that mRNA must be involved in consolidation of long-term memory.
 
only a structural change, like in synapse efficiency, could endure and that would require protein synthesis
 
Mice were trained but before the memory could form, puromycin in the hippocampus interfered. What a disappointment when the mice exhibited memory when the puromycin was washed out! If it did not block consolidation, what could puromycin have blocked?
 
should have blocked consolidation by blocking protein synthesis, but memories formed so it must have interfered with retrieval

A pigeon learns well in a Skinner box and then is retired for many years in a home cage. Placed back in the Skinner box for the first time after many years, what is the performance like and why?

it is at the level years earlier suggesting that forgetting is not as important as extinction

"There is more RNA in the hippocampus of a rat that has gained mastery in a T-maze learning task than in a control." Say something wrong with this statement as a summary of one biochemical basis of memory.

is it mRNA being referred to? mRNA does not store memories, it funcrions according to the mechanisms of central dogma, control experiments suggested that the difference was not due to learned behabior

Patient HM, with bilateral ablation of his hippocampi, can learn a mirror drawing task. What dichotomy of types of memory does this fact address?

procedural vs declarative

Why is a rat's performance in the radial 8-arm maze considered an example of "working memory?"

each time, it must remember which of the arms it has already visited

Beta and gamma secretases cut (what?) into (what?) relevant to memory.

amyloid precursor protein into beta amyloid

What did Hebb propose that reverberatin circuits were used for?

with excitation only such a loop could hold short term memory

How is it known that Brenda Milner's tragic subject (HM, with the bilateral hippocampal lesion) does have procedural (non-declarative memory)?
 
he can "learn" a mirror drawing task
 
Storage oscilloscope fragments were sprinkled on a regular oscilloscope. The entire physiology department at Yale wrote this spoof to criticize what published "finding?"

that RNA from a flat worm that had "learned" (or cannibalism) could transfer the memory
 
Explain why the term "working memory" applies to the radial 8-arm maze task.
 
withour any defined pathway, the rat knows which of the arms (s)he has visited so as to get all 8 pellets without repeating an arm
 
Nobody had the slightest idea what went wrong in Alzheimer's disease for decades. Now they have identified the involvement of several non-functional enzymes. What breakthrough paved the way for this important understanding?

finding familial inheritance allowed identification of genes

With some neural damage, you might forget word meanings but still retain practiced motor skills. How does your text characterize this dichotomy?

declarative vs procedural

You've just gotten electroconvulsive shock. What are you likely to have forgotten? (Hint, the answer is not "The answer to this question.")

events during the hour before, not your earlier life

Perhaps it is true that McConnell found that Planaria that ate Planaria that had been "trained" were trained in less trials. What legitimate criticism was leveled at the claim that memory was transferred through RNA?

no controls for sensitization

Answer either (1) What did Lashley mean by "engram?" Or (2) Where did he find it to be?

the memory trace, distributed with equipotentiality throughout cortex

Why do they use the expression "working memory" for performance in the radial 8-arm maze?

each time, animal can accurately remember which of the arms visited until (s)he reaches all of them

List at least one of the products of the five most obvious genes underlying familial Alzheimer's disease?

amyloid precursor protein, presenillins 1 & 2, apolipoprotein E, tau

Even though it has been over 50 years since his famous textbook, Donald Hebb is still mentioned frequently in neuroscience. In what context?

reverberating circuits of excitation for short term memory

Why did researchers put puromycin, an antibiotic, into the brain?

blocks protein synthesis

What is the precursor for the material that makes extracellular plaques in Alzheimer's disease?
amyloid precursor protein

What was the mental defect in Brenda Milner's famous patient HM, with lesions of the hippocampus?

anterograde amnesia

Name the intracellular accumulation product in Alzheimer's disease.

neurofibrillary tangles of tau

Although "memory transfer through cannabalism" [of RNA] was debunked in planaria, mRNA must be involved in long-term memory. By what mechanism?

in mediating any long term changes in synaptic function by protein synthesis

What does Lashley's "search for the 'engram'" have to do with memory and localization of function?
memory is stored everywhere with equipotentiality

Brenda Milner's famous subject, HM (who had hippocampal lesions) ,could not remember what had just happened but could learn to draw in a mirror. What famous distinction between types of memory is addressed?

declarative vs procedural

By what mechanism would Alzheimer's disease interfere with axon transport?

the hyperphosphorylated protein, tau, regulates microtubules

Mutations in Presenilin 1, Presenilin 2, and the E4 allele Apolipoprotein are genetic risk factors. Mutations in what other protein is missing from the above list of risk factors for the accumulation of beta-amyloid plaques.

amyloid precursor protein

"Presenilins are key mediators of Notch signalling." How does that relate to Alzheimer's disease?

enzymatic cleavage of membrane proteins is not just a pathological mechanism, it causes release of intracellular domains of important signalling proteins

In what nervous system compartment are neurofibrillary tangles?

inside neuron (axon)

How do you show that a rat with a hippocampal lesion is impaired in learning to find an underwater platform?

as repeated trials go by, latency to find it goes down for control not for lesioned

How do you show that HM's nondeclarative memory is not as bad as his declarative memory?

Can perform on mirror drawing task

***Synthesis

In rationalizing free will, what relationship does Nobelist Sperry assign to physical laws vs emergent properties?

physical laws still operate, but emergent properties outclass (supercede) them

What issue in neuroscience was Sperry attempting to address with his notion of emergent properties?

meaningful considerations in the meaning of human life such as free will are impossible to reconcile with a materialist view

Nobelist Roger Sperry was optimistic that people have free will even though materialistic science should dictate determinism. How did he rationalize this optimism?
 
although physical laws still apply, emergent properties of assembled systems have awesome possibilities

How does Sperry rationalize his faith in "the powers of perception, cognition, reason, and judgment" in human action and free will?

while physical laws still apply, there are emergent properties when the parts are assembled to the whole

"Lloyd Morgan's canon" is a fundamental statement in comparative psychology applied to what aspect of animal behavior?

whether consciousness is needed to explain behavior

According to Sperry, "the simpler ... molecular ... forces ... have been superceded." How then does he rationalize free will even though "materialistic science" would explain brain function in "biophysical terms."

because there are emergent properties of higher level configurations