Neuroscience 26
Exam 3
Spring, 2007
This is a closed-book, closed-note, 2-hour exam that is to be taken in Merrill 3 (Thursday
evening) or in our regular classroom (Earth Sciences 107) Friday morning. Write your answers
legibly in two different exam books - one for Prof. George=s part, and one for Prof. Baird=s
questions. On the cover of each book, write which part of the exam it is for, and write your
name. Each part is worth 50 points. Each starts with a recent abstract, followed by questions
about the abstract based on what we have been discussing recently in the course. Good luck!
Prof. George=s part: Abstract #1
Enriched environment treatment restores impaired hippocampal synaptic plasticity and
cognitive deficits induced by prenatal chronic stress.
Yang J, Hou C, Ma N, Liu J, Zhang Y, Zhou J, Xu L, Li L.
Neurobiology of Learning and Memory 2007 Feb; 87: 257-63.
Hippocampal synaptic plasticity, believed to be the mechanism underlying certain types of
learning and memory, can be affected by prenatal stress. Whether enriched environment
treatment (EE) in early postnatal periods can cause a recovery from these deficits is
unknown. Prenatal stress was evoked by 10 foot shocks (0.8 mA for 1s, 2-3 min apart) in
30 min per day given to pregnant female rats when fetuses were at gestational days 13
through 19. After weaning at postnatal day 22, experimental offspring were given enriched
environment treatment until being tested at 8 weeks of age; control offspring were exposed
to a normal cage environment. Electrophysiological and Morris water maze testing was
performed. The results showed that prenatal stress impaired long-term potentiation (LTP)
but facilitated long-term depression (LTD) in the hippocampal CA1 region in hippocampal
slices. Furthermore, prenatal stress exacerbated the effects of acute stress on
hippocampal LTP and LTD, and also impaired spatial learning and memory in the Morris
water maze. However, all of these deficits induced by prenatal stress were significantly
reduced or eliminated when animals were exposed postnatally to an enriched environment.
This work may contribute to the understanding of clinically important interactions among
cognitive deficit, prenatal stress and enriched environment treatment. Enriched
environment treatment during early postnatal periods may be one potentially important target
for therapeutic interventions in preventing prenatal stress-induced cognitive disorders in
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humans.
Notes: AEnriched environment@ means that instead of living in a boring cage isolated from other
rats and containing nothing but shavings on the floor, the experimental rats lived in cages with
running wheels, rubber objects to play with, and exposure to other rats.
Questions:
[1] The authors would like us to believe that stressing pregnant females affects the hippocampus
of the fetuses they are carrying, while the fetuses are still in utero. Suggest a criticism of this idea,
focussing on what might have happened to the rat pups during the 22 postnatal days before they
were weaned from their mothers. Suggest a change in experimental design that could eliminate
this objection. [6 points; suggested length: 2 sentences.]
[2] Why was the Morris water maze a good choice for testing learning and memory in this
particular experiment, rather than other well-established tests such as delayed non-matching to
sample? [4 points; suggested length: 2 sentences.]
[3] Describe briefly what the authors presumably did in the lab to study LTP in their experiment,
including what they presumably did to evoke LTP and what they did to measure it. [7 points;
suggested length: 3-4 sentences.]
[4] Hippocampal LTP involves one particular neurotransmitter and two classes of receptor for
that transmitter. (a) What neurotransmitter is involved? (b) If LTP is reduced in experimental
animals compared to controls, what is likely to be the difference after LTP induction between
experimentals and controls in terms of synaptic receptors? (c) If LTD is increased in
experimental animals compared to controls, again what is likely to be the difference in terms of
synaptic receptors? (d) What receptor type is involved in initiating LTP? [8 points]
[5] This paper didn=t deal with possible cellular and biochemical mechanisms by which
subjecting pregnant female rats to stress could affect their offspring=s neural plasticity later, and
mechanisms by which environmental enrichment could counteract these stress effects. Suppose
you wanted to follow up on this research by finding such mechanisms.
Questions:
(a) Assuming that stressing pregnant females does indeed affect the brains of the fetuses they are
carrying, suggest
(1) a plausible hormone that might be involed,
(2) a plausible effect the hormone might have on hippocampal neurons in the rat fetuses,
and (3) a plausible mechanism by which enrichment could act.
Briefly explain in each case why you think each suggestion is plausible. [ Part (a): 10 points]
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[There is a single best answer for (1), but several good possibilities for (2) and (3).]
(b) Suggest ways to test
(1) whether the hormone you named in (1) above is indeed involved,
(2) whether its effects are indeed what you hypothesized,
and (3) whether enrichment does have the effects you suggested.
[Part (b) 15 points; suggested length: 1 page total for question 5]
EXTRA CREDIT QUESTION: [1 point]: Which neurotransmitter specifically binds to GABA
receptors?
Prof. Baird=s part: Abstract #2. Answer in a separate exam book from Prof. George=s
part.
Differential effects of adrenalectomy on melanin-concentrating hormone and orexin A.
Drazen DL, Coolen LM, Strader AD, Wortman MD, Woods SC, Seeley RJ.
Endocrinology 2004 Jul;145: 3404-12.
Removal of glucocorticoids by adrenalectomy (ADX) reduces food intake and body weight
in rodents and prevents excessive weight gain in many genetic and dietary models of
obesity. Glucocorticoids play a key role to promote positive energy balance in normal and
pathological conditions, at least in part, by altering the sensitivity to hypothalamic peptides.
The hyperphagia after central neuropeptide Y administration, for example, is attenuated by
ADX, and there is evidence that glucocorticoids influence both MCH and orexin A activity. In
the present study, feeding responses to third ventricular MCH and orexin A were measured
in rats after bilateral ADX or sham surgery. ADX rats were significantly less sensitive to the
orexigenic action of third ventricular MCH, whereas orexin A-induced hyperphagia was
unaffected. Replacement of corticosterone in the drinking water of ADX rats reversed the
effects of ADX on MCH sensitivity. Although we found significant populations of
glucocorticoid receptors in the lateral hypothalamus, none were colocalized with either MCH
or orexin A-containing cell bodies. Furthermore, whereas ADX significantly reduced
hypothalamic MCH and orexin gene expression, this could not be restored by
glucocorticoids in the drinking water. Collectively, the present data suggest that
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glucocorticoids may promote food intake in part by potentiating the orexigenic actions of
MCH without affecting the actions of orexin A and that glucocorticoids act indirectly to
influence the effects of MCH on food intake.
Notes:
APositive energy balance@ = weight gain.
AHyperphagia@ / Aorexigenic@ = excessive eating; attenuated = Areduced@
MCH = melanin concentrating hormone
Agene expression@ refers to the fact that they labeled for MCH or orexin mRNA using in
situ hybridization.
Questions:
[6] 1) What is their hypothesis with regard to the relationship between glucorticoids and the
actions of the lateral hypothalamic peptides, MCH and orexin ? What conceptually similar
effects did we discuss with regard to the effects of leptin ?
[3 x 3] 2) a. Removing the adrenal gland would be expected to affect which of the thirst
and/or salt appetite related hormones that we discussed in class ?
b. What does this hormone do and what behavioral effect might the absence of this
hormone produce?
c. Could the possibility of such an effect provide an alternative explanation for the current
data ?
[8] 3) How do the current results fit in with the current model and more recent findings on
MCH and orexin function in the brain ? [be sure to describe the current model].
[6] 4) The results are not perfect. Describe the discrepancies of the behavioral effects with
the anatomical and with the mRNA results. Speculate on some possible explanations for
these discrepancies (there is no perfect answer).
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[3] 5) What is the importance of the sham surgery ?
[4] 6) Why did they put corticosterone in the drinking water ? Why might they not simply
inject it ?
[4] 7) Why do they conclude that glucocorticoids act only indirectly to influence the effects
of MCH on intake?
[10] 8) Discuss some follow-up experiments that you conduct to evaluate whether
glucocorticoids are truly affecting the MCH and orexin neurons in the brain. Use any (or
all !) of the methodologies that we discussed in class.
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