Page 1 Exam #4 2011 1 (6 pts). The amygdala is the crossroads for process ing sensory/environmental information associated with associative learning of aversive stimuli and the perception of alarm pheromones. a.Name “4” major “sensory systems” that send information to the lateral nucleus of the amygdala. b.The central nucleus of the amygdala (CNA) is its major output nucleus; what is the function(s) of the CNA’s output to the paraventricular nucleus of the hypothalamus? c. What is the function(s) of the CNA’s output to the lateral hypothalamus? 2 (2 pts). Classical conditioning of fear memory involves temporal pairing of a CS with a US. Give one example ofa CS, and one example of a US. 3 (3 pts). Postsynaptic neurons in the lateral nucleus of the amygdala undergo wha t form of synaptic plasticity during classical conditioned fear memory (what is the signaling pathway underlying this plasticity)? How can formation of this kind of memory be blocked? 4 (3 pts). Describe a famous h istorical example of conditioned fear memory in humans. 5 (2 pts). What is a symptom(s) and neuropathology of a patient with severe Urbach-Wiethe disease. 6 (2 pts). What is an “aha /eureka” moment? Give one example of an “insightful” vs. “non-insightful” problem? 7 (2 pts). What brain region(s) displays selective activation during fMRI analyses when an exp erimental subject solves a problem using insightful reasoning? 8 (3 pts). In general anatomical terms, what region(s) of the human brain is selectively activated (fMRI analyses) during visual word recognition? What remarkable discovery has been made ab out this region in the brains ofilliterate Chinese farmers? 9 (2 pts). Name “1” similarity and “1” difference in the cellular/molecular signaling pathways that underlie the perception of “odors” vs. “pheromones”. 10 (2 pt). What region(s) in the human brain is selectively activated (fMRI analyses) during perception of “alarm” pheromone(s)? 11 (2 pts). When first time skydivers were analyzed for their perception of ambiguous/threat faces, how did theirresponses differ when they inhaled “exercise” vs. “alarm/stress” sweat? 12 (2 pts). What was the first pheromone identified? What is its function? 13 (2 pts). What is the function of the VNO in most n on-primate mammals? 14 (2 pts). What is the function of the VNO in humans? 15 (1 pt). What year did Dr. Archimedes receive the Nobel Prize in Physiology and Medicine? 16 (3 pts). What is the most compelling experimental evidence that inhibition of PKM-zeta disrupts memory “storage” and NOT memory “retrieval”?
17 (3 pts). Describe “3” cellular and/or molecular mechanisms by which LTD can decrease synaptic strength.
18 (3 pts). During the induction and maintenance of LTP there is a positive feedback loop that increases PKM-
zeta’s activity. Briefly describe this feedback loop; “START” your description at the level of PKM-zeta mRNA.
19 (2 pts). What are the “distinct” biochemical properties of the “ZIP” pseudosubstrate inhibitor of PKM-zeta that
allows it to work in vivo?
20 (2 pts). The in vivo perfusion of ZIP into the hippocampus (bilaterally) 22 hours after the induction of LTP:
a. Erases LTP
b. Increases EPSP amplitudes at CA1 synapses
c. Coverts LTP to LTD at CA1 synapses
d. Increases spatial memory retention in rats
e. Decreases synapse formation in the CA1 region
f. Increases insightful problem solving in rats
21 (3 pts). Why was it so terribly important to develop the transgenic technology to produce a conditional knock-out
of neuronal NMDA-R1s in the CA1 region of the hippocampus? Make sure you describe the properties of this
“conditional” knockout in your answer.
22 (3 pts.). Discoveries by Kristin Harris (using serial EM reconstructions) showed that LTP promotes a specific
change in synaptic/dendritic ultra-structure in the hippocampus. What did she show? [Use a figure if it helps.]
23 (4 pts). We discussed the associative property of LTP in experiments using two independent synaptic pathways
(strong vs. weak) that converge on the same postsynaptic neurons. Describe the mechanism by which tetanic
stimulation to the weak pathway induces LTP in the weak pathway “only” when it is paired with simultaneous
tetanic stimulation to the strong pathways.
Bonus Question (2 pts). Give one real-world practical example about how selectively inhibiting PKM-zeta in a
specific brain region in humans could be beneficial in the context of brain diseases or neurological disorders.
Bonus Question (2 pts). Give one real-world practical example about how exploiting the neurobiology of
pheromones could be very beneficial to humans in the global community. [The pentagon’s development of a
pheromone “bomb” is NOT an acceptable answer.]
Exam #4 20108 (3 pts.). What is/are the major property(ies) of a “silent” synapse?
9 (3 pts). We discussed the associative property of LTP in experiments using two independent synaptic pathways
(strong vs. weak inputs) to the same postsynaptic neuron. What is the basic mechanism by which tetanic stimulation
to the strong pathway induces LTP in the weak pathway when tetanic stimulation is simultaneously delivered to both
pathways?
10 (2 pts.). LTP displays ALL of the following similarities with “learning and memory” EXCEPT:a) LTP is stimulus-dependent (e.g., induced by tetanic high-frequency stimulation)
b) LTP-dependent increases in synaptic strength have been shown to last for many years in humans
c) LTP is rapidly induced
d) LTP is associative (i.e., similar to Pavlovian conditioning)
e) LTP is pathway/input specific
11 (2 pts.). ALL of the following statements characterize LTP and/or LTD EXCEPT:
a) LTP and LTD induction involves the activation of AMPARs
b) the induction LTD results in the disappearance of silent synapses
c) the induction of many types of LTP/LTD requires NMDAR activation
d) LTD induction involves repetitive (e.g., 1 Hz stimulation for ~10 min) and small (<1 µM) increases in postsynaptic Ca2+ levels
e) LTP induction requires short (<1 sec) but large increases (>5 µM) in postsynaptic Ca2+ levels
22 (3 pts). Sacktor and colleagues made many discoveries about the role of PKM-zeta in synaptic plasticity. The
figure below shows EPSCs recorded from a postsynaptic neuron during injection of PKM-zeta. Injection of PKM-zeta for 10 min produced synaptic potentiation. A tetanus (100 Hz, 1 sec) delivered to the neuron at 10 min
produced “no” additional synaptic potentiation. This phenomenon is called “occlusion”. What does “occlusion”mean at the level of molecular signaling pathways and synaptic plasticity?
23 (2 pt.) True or False. Following spatial learning, inhibition of hippocampal PKM-zeta disrupted both spatial
memory “storage” and “retrieval”.
25 (3 pts.). Sacktor and colleagues carried out two sets of experiments showing that PKM-zeta activity in the
amygdala is important for establishing “avoidance” and “classical conditioned fear” memories. Carefully describe
“ONE” of these two experiments and the results, and specify what kind of memory was disrupted.
Bonus question (3 pts.). When tetanic (high frequency) stimulation is delivered to a presynaptic terminal (upper
panel below) and post-tetanic potentiation of EPSPs is observed in the postsynaptic neuron (lower panel below),
what is the primary mechanism that causes this increase in postsynaptic responses (i.e., increases in EPSP
amplitudes) to last long after tetanic stimulation has ended?
Time
12 (2 pts.). Give one example of explicit, and one example of implicit memory.
19 (3 pts.). In transgenic mice with the conditional knockout NMDA-R1s, what is distinct about glutamatergic
excitatory synapses on their hippocampal CA1 pyramidal neurons?
20 (3 pts.). Describe how transgenic mice with the conditional knockout NMDA-R1s performed in the “transfer
test” following their training in the Morris water maze?
21 (3 pts.). Clive Wearing suffers from brain damage following Herpes virus encephalitis. Briefly describe Clive’s
cognitive dysfunction.
Exam #4 5-11-09
4 (3 pts). What is the major property of “silent” synapses?
5 (6 pts). Describe the two strains of transgenic mice that were crossbred to produce the “conditional”
knock out of NMDA-R1s. How is hippocampal LTP altered in these knock-out mice? How well do the
knock-out mice perform in the “transfer test” following training in the Morris water maze?
6 (5 pts). We discussed the associative property of LTP in experiments using two independent synaptic pathways
(strong vs. weak inputs) to the same postsynaptic neuron. Describe the mechanism by which tetanic stimulation to
the strong pathway induces LTP in the weak pathway only when tetanic stimulation is simultaneously given to both
pathways.
7 (5 pts). Describe the experiment using “caged” glutamate, which showed that activation of synaptic GluRs
caused structural changes in neurons. What neuronal structures changed following glutamate “uncaging” ?
8 (6 pts). There are important presynaptic changes associated with the induction of LTP. Describe the experiments
and results which demonstrated that changes in presynaptic “release probability” contribute to synaptic
strengthening.
9 (6 pts). What is/are the basic difference(s) in signaling pathways that allows activation of postsynaptic NMDA-Rs
to induce LTP under certain conditions, vs. LTD under other conditions?
10. This is a “two” part question.
PART ONE (4 pts): Clive Wearing suffers from severe brain damage. What was the cause and extent of
Clive’s brain damage?
PART TWO (4 pts): Describe the overall learning and memory deficits that Clive experiences?
11 (5 pts). What is the basic sequence of events that involves postsynaptic GluRs and signaling pathways to induce
LTP following tetanic stimulation of Schaffer Collateral axons in the hippocampal CA1 region?
13 (THREE PART QUESTON). Todd Sacktor and colleagues have made several discoveries about the role of
PKM-zeta in synaptic plasticity, learning and memory.
PART ONE (4 pts). Describe the basic mechanisms that regulate PKM-zeta during the induction of LTP.
PART TWO (5 pts). Describe the basic testing and training protocols that Sacktor and colleagues used to show
that inhibition of hippocampal PKM-zeta disrupted spatial memory “storage” and not memory “retrieval”.
PART THREE (5 pts). Sacktor and colleagues carried out two sets of experiments showing that PKM-zeta activity
in the basal-lateral nucleus of the amygdala is important for certain kinds of memory. Carefully describe “ONE” of these experiments and indicate what kind of memory was disrupted.
