"Throw Mama from the train a kiss, a kiss
And she throws one back from up high"
-Irving Gordon (Patti Page)
Purves et al., Chapter 31
Chapters 8 and 24 dealt with "learning" at the cellular level,
sort of an extension of development.
Consider how important memory is in defining the human experience.
In many ways, memory seems to be like an input to the CNS, as significant
as the only real input, namely sensory input.
Probably most believers' concept of an after-life relies on memories being
In many ways memory formation is a continuation of development.
Forgetting (?) - intuition indicates how widespread forgetting is, but,
when operant conditioning dominated American psychology, forgetting was
denied - only extinction (sort of an "unlearning") existed.
Dementia - Alzheimer's syndrome is a reminder as to how fundamental memory
is to the quality of human life.
The entire literature empahsizes short- and long-term memory.
Amnesia is informative: "retrograde" for period long ago (rare)
vs. anteriograde, cannot learn new.
Recent memory loss, a patient might know how to play cards but not know
how (s)he came to be playing that particular game.
Fig. 31.1, p. 696
Chapter emphasizes declarative memory (for facts, possibly involving language)
and procedural (skill, practiced skills) memory.
Extraordinary memory of Luria's subject Sherashevsky.
Famous patient HM studied by Brenda Milner - lesion temporal lobe + hippocampus
and amygdala at age 27 for epilepsy [grand mal seizures]- has anteriograde
amnesia -after 50 yrs of study Milner still has to introduce herself - but
HM can learn mirror drawing task (procedural memory).
Landmark Paper: WBScoville & B Milner, Loss of recent memory
after bilateral hippocampus lesions, J Neurol Neurosurg Psychiat 20, 11,
1957, see also J NIH Res 8, 42-51, 1996
Another subject - NA, lesion [accidentally stabbed by roomate playing with
fencing] of dorsomedial thalamus, mammillary bodies, right medial temporal
lobe - amnesia like HM.
Another, RB, had ischemia with only loss of hippocampus, verified after
presumably something electrical like Hebb circuits - easily disrupted,
say, by electroconvulsive shock (used to treat depression).
Then there must be a consolidation for the sake of long-term memory which
must involve permanent changes like changes in synapses. mRNA and protein
MUST mediate change.
Retrieval is an important consideration.
Long term memory-
Biochemistry of memory got off to a terrible start
Classic (bad) papers
R. Thompson and J.V.McConnell (1955) Classical conditioning in planarian,
Dugesia dorotocephala, J. Comp. Physiol. Psych. 48, 65-68.
Poor controls, not replicated
J.V.McConnell, (1962) Memory transfer through cannabalism in planarium,
J. Neuropsychiat. 3 suppl 1 542-548 (eat RNA of worm that has learned, then
worm knows it already)
Classic (spoof) paper
J. G. Nicholls, D. A. Baylor et al.. (i.e. the whole physiology department
at Yale), Persistence transfer, Science 158, 1967:
...demonstrate the transfer of certain innate characteristics from one oscilloscope
to another. Accordingly, a Tektronix Storage oscilloscope (RM 564)...was
pounded with a Sears ball peen hammer (Cat. No. 28B4652) on a Fischer Lab
bench (Cat. No. B158)...until all electronic components and the tube were
reduced to sufficiently small pieces to pass through a filter made of 007-mesh
nylon stocking (seamless). The storage oscilloscope fragments (SOF)...sprinkled
over the chasis of a Tektronix 502 oscilloscope. The persistence of the
afterglow was used as an index... In 18 of 33 experiments, there was an
increase which was highly significant (,.001, t-test). While the average
increase in persistence was not large - 3.2 msec - it nevertheless suggested
that some change had been wrought in the recipient oscilloscope by the SOF.
(also a 1970 movie) Hauser's
memory, describes events after a dead spy's RNA is transferred to gain his
One of the professors whose work I had to learn (to pass my Ph.D. exam)
worked in this area. His graduate student was in my peer group. His research
involved quickly dissecting the brain after teaching a rat in a T-maze and
showing that RNA in the hippocampus changed. Before he was finished, his
work was on control experiments showing that these changes might not be
attributed to the maze learning experience.
In summary, RNA experiments were naively done with great optimism &
B. W. Agranoff Memory and protein synthesis, June 1967 Scientific American,
long term memory must involve something like protein synthesis L. B. Flexner
et al. Memory in mice analysed with antibiotics, Science, 155, 1967, 1377-1383
antibiotics like puromycin block protein synthesis
but return of memory with saline washout suggests interference with retrieval
How is memory stored in the brain?
Fig. 31.9, p. 706
How and where are memories stored?
Lashley - search for engram - found "equipotentiality" [in cortex]
(vs. localization of function)
Pribram - it is like
a hologram - everything is stored a little bit everywhere (lasers and holograms
were popular science in the 1960s; half a hologram has all the information
of the whole hologram, but degraded -- you have to "look around the
corner" to see everything.).
The temporal lobe seems particularly important for establishment, but not
Penfield - electrical stimulations
Working memory for spatial location
Fig. 31.10 p 707
Animal model of "working memory" - radial 8 arm maze put a food
pellet on the end of each arm and rat uickly learns to visit each arm one
time before any repeats - David Olton - rat has amazing spatial memory and
hippocampal lesion disrupts that.
Personal reflection - he was an associate professor where I was an
assistant professor; this demonstration, that became standard in many learning
labs across the country, was the undergraduate project of Robert Samuelson,
an undergraduate student, and was made by 2x4's thrown together in the wood
shop. Although Scientific American was known to publish mostly articles
invited from famous people, Dave broke the mold by submitting the paper
(Spatial memory, June 1977, 82-98) that made their work known even in undergraduate
courses across the country.
Box 31D - pp. 713-714
Alzheimer's disease - neurofibrillary tangles (tau) in cells and amyloid
plaques (BA) outside cells -
5% are familial early onset -
beta amyloid precursor protein mutations on chromosome 21 (695-770 aa long.
beta and gamma secretase cut to 42 aa fragment - bad-
presenillin 1 on chromosome 14
presenillin 2 on chromosome 1
also apolipoprotein E (E4 allele) varient (on chromosome 19) predisposes
tau on chromosome 17
There is lots more information and it pours in fast these days.
several recent student presentations
Recent paper G Miller Computer game sharpens minds, Science 310,
Can mental exercise help?
Garden view care center activity based dementia care
Exam questions from 2005 - 2012 relating to this outline
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
"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
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
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?
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
How do you show that HM's nondeclarative memory is not as bad as his declarative
Can perform on mirror drawing task
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