The first lecture outline

Historical Introduction


Purves et al., Chapter 1 and figures from Chapters 6 & 27 and Appendix
(there will also be a review that introduces you to the Sylvius CD)

(some of this is a review of "Bio 1" and "Cell biology")

Brain - ancient history

Hippocrates (460-379 BC), of "hippocratic oath" fame, understood the influence of the brain in determining normal and abnormal functions, emotions, learning, insanity.

Appendix Fig. A23A, p. 743

(this human brain view shows cerebrum, cerebellum, ventricles)
Galen (AD 130-200) did careful dissections. He thought, from texture, that the cerebrum was sensory and cerebellum was motor. This was remarkably (not completely) correct, though for the wrong reasons. There was interest in the ventricles (filled with cerebro-spinal fluid [CSF]) secreted by choroid plexus, and this fit in with belief in vital "humors."

Neuroanatomy terms:

Appendix Fig. A10A p. 728
(view of exterior of human brain)
sulcus (plural=sulci) = fissure
For instance, central sulcus is major landmark
gyrus (plural=gyri) = convolution -> lobes (a larger area)
For instance, precentral gyrus is motor cortex
And postcentral gyrus is somatosensory (touch) cortex

Appendix Fig. A3 p. 720
(colored view of exterior and mid-sagittal section of human brain)
Emphasis is on "localization of function" in different lobes
For instance, occipital lobe is where vision projects
And Temporal lobe is where audition projects

TRANSPARENCY shows the version of this picture the Biology Department teaches to freshmenjust to put into perspective the degree to which much of this information is background,

CNS = central nervous system (brain and spinal cord)
PNS = peripheral nervous system

Appendix Fig. A14 p. 734
(human brain drawing showing coronal sections, to reveal basal ganglia)
shows the coronal sections indicated
white matter, bundles of myelinated axons (Tracts in CNS, Nerve in PNS)
[misnomer - optic "nerve," second cranial nerve, is actually a tract since retina and optic nerve are considered part of the CNS on embryological grounds]
and
gray matter (Nuclei in CNS, Ganglia in PNS)
[misnomers - basal ganglia are nuclei and ganglion cells in retina]

Fig 1.9 p. 13
(cross section of human spinal cord)
white matter and gray matter
(nerve connections to and in the spinal cord)
Nerve (peripheral nervous system [PNS])
Tract (central nervous system [CNS])

Fig. 1.7 p, 12
(diagram of knee jerk reflex)
Afferent (toward CNS)- Efferent (away from CNS)

Appendix Fig. A12A p. 730
This shows a mid-sagittal section
Decussation- crossing of fibers
The biggest is the corpus callosum

Appendix Fig. A1A p. 718
(brain with directions drawn in)
Rostral (toward the front)- Caudal (toward the back)
Superior (above) Inferior (below)
(not shown) Lateral - Medial

Appendix Fig. A1B p. 718
(brain with sections drawn in)
Coronal (would be cross section if human brain were anterior)
Horizontal vs Sagittal - (would be like longitudinal sections)

Some more recent historical figures and issues

Appendix Fig. A17A p. 738
(blood supply of brain)
Thomas Willis (1621-1675) (English) circle of Willis
fed by both internal carotids, a block would not deprive half of brain of blood supply

Here is the equivalent picture from our sheep brain dissection

Fig. 27.1 p. 610
Pierre-Paul Broca (1824-1880) (France) brain surgery
patient with damage in left hemisphere shows speech loss => lateral localization
vs. Lashley (cortical lesions in learning experiments) mass action and equipotentiality

In the old days, stroke (defects while living and damage in post-mortem) was the way to make conclusions in humans; now there are imaging techniques.
In animal models, stereotactic lesions can be made.
Electrical stimulation can also be applied, and, in general, it has the opposite effect of lesioning.

Fig. 27.2 p. 611
(Brodmann areas drawn onto human brain)
Korbinian Brodmann (early 20th century) has lots of brain areas with numbers
famous ones: 17-vision, 4-motor, based on cellular cytoarchitecture

Stroke

Current affairs
Jan 5, 2006, Israel's premier Ariel Sharon has a stroke complicated by being on blood thinners.
Box B, Appendix p. 735
Brain's need of oxygen makes interruption in blood flow dangerous
3rd leading cause of death in US
(1) thrombus (local occlusion) 50%
(2) embolus (object in blood stream) 30%
(such interruption in blood supply is called "ischemia")
(3) hemorrhage (e.g. from aneurism) 20 %
Tissue plasminogen activator (TPA) to dissolve clot
Recent reading: CM DeLude "Widening the window" (news scan, medicine) pp 21-22 Scientific American August 2005
Few get TPA because they come in too late for it to be effective (<3 hr)
If neurons are not dead, TPA may still work; newer CT and MRI scans can now show this.
Giving oxygen also buys time.
New drug: Desmoteplase (from vampire saliva) like TPA (breaks fibrin) but more potent and selective.

Structure of the Nerve cell

Fig. 1.2F - p 4
(Purkinje cell)
1836 Jan Purkinje (Czech) - Purkinje cells in cerebellum - these are highlighted with Golgi (see below) staining

Fig. 1.7 p. 12
(diagram of knee jerk reflex) [again]
1865 Otto Deiters (Bonn) - motor neuron

Fig. 1.3A p. 6
(cells and connections in brain)
axis cylinder -> axon, dendrites (branches)
reticular theory (connected like blood stream) vs. cell theory (cells are separate)
1885 Camillo Golgi (Italy) - potassium dichromate fix silver impregnation, still believed reticular theory
1888-> Santiago Ramon y Cajal - real thorough descriptions of many systems, believed in cell theory
1906 Nobel Prize in Physiology and Medicine for "the structure of the nervous system"

Advancements in cell anatomy methodology

Figs 1.3, 1.4, 1.5 & 1.6 are amazing preview of many semester topics

Beyond the level discussed above, tracts could be found by dissection. Looking ahead to the sheep brain dissection, this tract dissection of the midsagittal cut reveals the fornix, the mammilo-thalamic tract and the habenulo-peduncular tract. See slide 11

Fluorescence. Excitation with short wavelength. While electron is in excited state, there is some radionless de-excitation. When electron comes to ground state, it has less energy, so photon emitted has less energy (longer wavelength).

Here is a fluorescence microscope.
Short wavelength comes (through color filters) from above, hence "epi-illumination" or "incident illuminator."
Of course, there is a camera.

Fig. 6.11A p. 127
In the 1960s there was a lot of excitement about how specialized techniques (histochemical fluorescence) allowed researchers to trace the pathways used by a specific neurotransmitter substance. Fig. 6.11 shows dopamine pathways from the substantia nigra to the striatum and the cerebral cortex.

Fig. 1.6 E-H p. 11
Nissl stain shows cells (like cell layers in cortex)

Fig. 1.6 A,B p. 11
Golgi technique only colors a few cells so they can be viewed in their entirety.

Fig. 1.6 C p. 11
a fluorescent dye can be injected.

Here is a figure I prepared to explain how antibodies could be used in the electron microscope to localize proteins. The protein is an antigen. An antibody, binds to an epitope on the protein. A secondary antibody with an electron dense attachment (colloidal gold for electron microscopy or a fluorescent label for fluorescence microscopy) binds the antibody. Here is a figure I found subsequently) in this very useful site.

Here is a micrograph where Rh1, the rhodopsin of one type of photoreceptor in the Drosophila compound eye, is labeled ("decorated") with immunogold (Sapp et al, J. Neurocytol. 20, 597-608, 1991)

Here is a laser scanning confocal microscope, a fancy fluorescence microscope.
This machine is from a grant obtained by Prof. Spencer (and a few others of us).
For a light source, a laser is used.
Light is measured and fed to a computer for image acquisition.
Low depth of field (only one plane is in focus) provides "optical sectioning"
Images are very clear.

Here is Rh1 labeled with a fluorescent antibody in the confocal

Fig. 1.4 A p. 8
Tau (red) (microtubular binding protein in axons) accumulates in Alzheimer's, tubulin (green) in cells

Fig. 1.4 B p. 8
Developing cell in culture has actin (red) in growing tips.

Confocal

Because of "optical sectioning," (low depth of focus) many planes in a "z-stack" can be put into a Quick-time movie, [and this one shows disorganization of rhabdomeres, indicative of degeneration, where R1-6 rhabdomeres are labelled with GFP]

Review utilizing Sylvius

An access code came with your book
Launch Sylvius , Launch Visual Glossary
and we will use it for various views of :
Broca's area, Wernicke's area, motor cortex, auditory cortex
Brodman's areas, famously 4 (precentral gyrus=motor cortex), 17 (visual cortex)
Occipital lobe
Postcentral gyrus
Spinal cord (including cervical and lumbar enlargements of gray matter for fore- and hind-limbs
Striatum
Substantia nigra

Brain imaging techniques

(Box 1B - three pp. 18-19) MRI

Suggested readings

Marcus E Raichle (WashingtonUniversity Radiology and Neurology) The brain's dark energy, Scientific American March 2010 44-49. Current research on brain imaging, mental function and disorders.

Thomas R. Insel (National Institute of Mental Health) Faulty circuits, Scientific American April 2010 44-51. About mental disorders and brain circuits.

Alumnus research in neuroscience

Adrian A. Epstein, SLU class of 2002, took this course from me in 2002 (and introductory biology earlier). After that, he went to Washington University and was a research assistant in biological imaging (in the Department of Radiological Sciences). He is first author of several abstracts (convention presentations) and is coauthor of J. S. Shimony et al., Diffusion tensor imaging reveals white matter reorganization in early blind humans, Cerebral Cortex, 2006. Here, they use a specialized technique called diffusion tensor imaging to trace tracts (hence DTT= diffusion tensor tractography) to compare the visual projection in normal and blind subjects. Now he is in the MD-PhD program at Nebraska.

Some useful information and links

As of January, 2014, Neuroscience in SLU's A&S College is a contract major (with limited enrollment and no funding) web site. Neuroscience at SLU's Medical school is in the Center of Anatomical Science and Education and Department of Pharmacology-Physiology. Outlines from my signal course in biology might be helpful sometimes. Dr Buchanan in Psychology works in cognitive neuroscience of stress. Dr Kirchhoff's neuroscience interests are briefly encapsulated in the SLU Psychology site. Dr. Anch in Psychology teaches 4 courses in physiological psychology relevant to Neuroscience, PSY-A415-01: Science of Sleep, PSY-A513-01: Advanced Physiological Psychology, PSY-A413-01: Physiological Psychology, and PSY-A414-01: Drugs and Behavior. There is a philosophy professor, Dr. Terzis, who teaches a relevant course PL A-482-01 "Biology and Mind" which is relevant to this topic.

Here are some web sites for your present and future reference:
A professor I had my first year in graduate school has an extensive web site on Biology of the Mind
Society for Neuroscience
Neurosciences on the internet


Exam questions from 2005 - 2012 related to this outline

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

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