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Exam #4 2011
1 (6 pts). The amygdala is the crossroads for processing 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 CNAs output to the paraventricular nucleus of the hypothalamus?

c. What is the function(s) of the CNAs 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 of a CS, and one example of a US. 3 (3 pts). Postsynaptic neurons in the lateral nucleus of the amygdala undergo what 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 historical 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 experimental 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 about this region in the brains of illiterate 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 their responses 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 non-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?

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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 PKMzetas 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 pentagons development of a pheromone bomb is NOT an acceptable answer.]

Exam #4 2010
8 (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

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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 M) increases in postsynaptic Ca2+ levels e) LTP induction requires short (<1 sec) but large increases (>5 M) 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 PKMzeta 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?
1 Hz
10 Hz

Time

12 (2 pts.). Give one example of explicit, and one example of implicit memory. 13 (2 pts.). What is a quantum (plural: quanta)?

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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 Clives 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 Clives 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.

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24 (2 pts.). Discoveries by Kristin Harris and colleagues showed that LTP promotes the formation of new dendritic spines. Which of the two mechanisms shown in the figure below is most consistent with their results?

A
SC
(cross section)

sdMSB

B
SC

PreSpine splitting

Pre-

sdMSB

Axons

Spine sprouting

PreSC

PreSC

Split-a-Spine

Sprout-a-Spine