Deck 10: Memory, Learning, and Synaptic Plasticity

Question 1

Why was AP5 applied while the neuron was held at +30 mV?

Answer 1

This was a control to show that the responses generated at +30 mV were from NMDARs. Depolarizing the neuron to +30 mV could have activated a different voltage dependent current and not NMDARs.

Question 2

What is the basic circuitry of the hippocampus?
(a) Entorhinal cortex > ______ (area) via the ________ path
(b) ________ (cell layer) to ______ (cell layer) via the ___ (pathway)
(c) __________ (cell layer) to _______ (cell layer) via the ______ (pathway)
How Is Synaptic Plasticity Achieved?

Answer 2

(A)
Entorhinal cortex > dentate gyrus (area) via the perforant path
(b) Granule cell (cell layer) to CA3 (cell layer) via the mossy fiber (pathway)
(c) CA3 (cell layer) to CA1 (cell layer) via the Schaffer collateral (pathway)

Question 3

Which is true for spike-timing-dependent plasticity? Select all that apply.
(a) If a postsynaptic neuron repeatedly fires action potentials before a presynaptic neuron, the synapse is potentiated.
(b) If a presynaptic neuron repeatedly fires action potentials before a postsynaptic neuron, the synapse is depressed.
(c) If a presynaptic neuron repeatedly fires action potentials before a postsynaptic neuron, the synapse is potentiated.
(d) If a presynaptic neuron fires action potentials more than 100 ms prior to the postsynaptic neuron, the synapse is depressed.
(e) If a postsynaptic neuron fires action potentials more than 100 ms after the presynaptic neuron, the synapse is depressed.

Answer 3

(C)
If a presynaptic neuron fires an action potential within ~50 ms of an action potential in the postsynaptic neuron the synaptic efficacy will increase. If the postsynaptic neuron fires ~50 ms prior to an action potential in the presynaptic neuron the synaptic efficacy will decrease. More than 100 ms in between action potentials is too long in time to have coincident activity and the synaptic weight will remain the same.

Question 4

The amnesic patient, H.M., lost the ability to store new memories, but could still remember events and people prior to his surgery. What kind of memory did he lose? Choose all that apply.
(a) Explicit memory
(b) Implicit memory
(c) Long-term memory
(d) Short-term memory

Question 5

Figure Q10-7 shows data from one of the first experiments demonstrating LTP by Bliss and Lomo (1973). The arrows indicate points at which high frequency stimuli were given. Figure Q10-7
A. Figure Q10-7A below depicts an example of a field EPSP prior to high frequency stimulation. The vertical line is the stimulus artifact. What would the fEPSP look like at 1 hour and 4 hours? Figure Q10-7A
B. What would happen to the response if Bliss and Lomo had given a low frequency stimulation of about 1 Hz at 5 hours?
Question 10-8 and 10-9 refer to (Figure Q10-8) below. Figure Q10-8 shows a synaptic matrix, which describes how changes in synaptic weight can contribute to memory storage. There are presynaptic inputs A-E and postsynaptic outputs I-IV. Figure Q10-8

Question 6

The amnesic patient, H.M., could still learn motor tasks, like learning to draw while looking in a mirror. What kind of memory is this? Choose all that apply.
(a) Explicit memory
(b) Implicit memory
(c) Habituation
(d) Sensitization

Question 7

What is synaptic plasticity?

Question 8

Which is an example of associativity? Select all that apply.
(a) Input neurons A and B fire a burst of action potentials simultaneously.
(b) Output neurons I and II fire a burst of action potentials simultaneously.
(c) Input neurons A and B fire a burst of action potentials at the same time that output neurons I and II fire a burst of action potentials.
(d) Input neurons A and B fire a burst of action potentials at the same time that output neurons I and II are depolarized.
(e) Input neuron C fires a burst of action potentials at the same time that output neuron II is active.

Question 9

H.M. could still learn a motor task. The following is a figure showing how H.M improved in his ability to trace an image over three days. If he was able to learn the motor task, but his long-term memory of learning the motor task was impaired, what do you think his performance on day 2 would look like? Figure Q10-3

Question 10

Why is CaMKII a good candidate for a molecular memory molecule?

Question 11

What is long-term potentiation?

Question 12

Figure Q10-15 illustrates the data from one of the original experiments that showed evidence for 'silent synapses'. CA3 axons were stimulated while the postsynaptic response when the CA1 neuron were voltage-clamped at -65 mV. Figure Q10-15
A. Why were the CA1 neurons held at -65 mV?
B. What happened when the CA3 axons were stimulated before pairing, in which the presynaptic CA3 neurons were stimulated while the CA1 neurons were depolarized and what are two reasons for the result?
C. What happened when the CA3 axons were stimulated after 'pairing' and what was the interpretation of the result?
D. Summarize the idea of 'silent synapses' as a form of synaptic plasticity. Include the basic conclusions drawn from the experiments outlined in this and the previous experiment.

Question 13

What are 'silent synapses'? Select all that apply
(a) Synapses with no postsynaptic receptors
(b) Synapses in which neurotransmitter is not released from the presynaptic neuron
(c) Synapses with only NMDARs in their postsynaptic surface
(d) Synapses with only AMPARs in their postsynaptic surface
(e) Synapses in which AMPARs are inserted into the postsynaptic surface

Question 14

Why does the NMDAR provide a good molecular mechanism for coincidence detection? Select the best answer.
(a) It is the receptor for glutamate, the major excitatory transmitter in the brain.
(b) It requires depolarization to remove the Mg²⁺ block.
(c) It allows Ca²⁺ into the postsynaptic neuron.
(d) The NMDAR channel can remain open for long periods of time.
(e) It is expressed in the hippocampus.

Question 15

How is LTD generated? Choose all that apply.
(a) High frequency stimulation
(b) Low frequency stimulation
(c) Increase in intracellular Ca²⁺
(d) Activation of CaMKII

Question 16

In an experiment that showed that CaMKII was involved in synaptic plasticity, one input was stimulated at high frequency (S1), which induced LTP. LTP was not induced from a second input that was not stimulated at high frequency (S2). Later in the same experiment, constitutively CaMKII was injected into the cell body of the postsynaptic neuron and both inputs were stimulated. Stimulation of which input resulted in LTP and why? Choose all that apply.
(a) Stimulation of S1 induced LTP because those synapses were already potentiated.
(b) Stimulation of S1 did not induce LTP because it was occluded by prior LTP.
(c) Stimulation of S2 induced LTP because of the presence of CaMKII that was paired with S2 stimulation.
(d) Stimulation of S2 did not induce LTP because it was not previously potentiated.

Question 17

Below is a figure showing LTP that was induced by high frequency stimulation (indicated by the arrow) at 0 minutes (traces 1 - 3). Figure Q10-11
A. What would happen to LTP if the NMDARs were blocked with APV? Which trace would be generated?
B. What would happen if an NMDAR with a higher ion channel conductance than normal was expressed in the postsynaptic cell? Which resulting trace would be generated?

Question 18

In the sentence below, circle the correct terms.
LTD and LTP represent a continuum of modifications of synaptic strength. Low-frequency stimulation results in DEPHOSPHORYLATION/PHOSPHORYLATION of AMPA/NMDA receptors, which results in ENDOCYTOSIS/EXOCYTOSIS of the receptors. This results in synaptic DEPRESSION/POTENTIATION.

Question 19

Which is an example of cooperativity? Select all that apply.
(a) Input neurons A and B fire a burst of action potentials simultaneously.
(b) Output neurons I and II fire a burst of action potentials simultaneously.
(c) Input neurons A and B fire a burst of action potentials at the same time that output neurons I and II fire a burst of action potentials.
(d) Input neurons A and B fire a burst of action potentials at the same time that output neurons I and II are depolarized.
(e) Input neuron C fires a burst of action potentials at the same time that output neuron II is active.

Question 20

Why was the postsynaptic CA1 neuron voltage clamped to +30 mV? Select all that apply.
(a) To stimulate insertion of AMPA receptors into the postsynaptic membrane
(b) To move NMDA receptors into the synapse from an extrasynaptic site
(c) To cause coordination between the pre- and postsynaptic neuron
(d) To increase conductance of the NMDAR by removing the Mg²⁺ block
(e) To stimulate AMPA receptors, which in turn activate NMDA Rs

Question 21

For the graph on the right, the anterior cingulate cortex (ACC) was inactivated with lidocaine 1, 3, 18, and 36 days after fear conditioning training. What happened to these rats compared with the controls?
(a) The rats with ACC lesions did not remember the association of the location and the shock with increased delay from training.
(b) The rats with ACC lesions remembered the association between the location and the shock for a longer time from training than the control rats.
(c) The rats with ACC lesions learned the task faster than control rats.

Question 22

Taking together the results in Figure Q10-37, what is the interpretation of these results?

Question 23

Figure Q10-23 shows an example of endocannabinoid modulation of synaptic strength after high frequency stimulation (indicated by the horizontal bar above the large amplitude activity) to the presynaptic CA3 neurons. What would happen to the response if the CB1 receptors were blocked? Figure Q10-23
(a) The frequency of spontaneous IPSPs immediately after the stimulus would decrease compared to their frequency prior to the stimulation.
(b) The frequency of spontaneous IPSPs immediately after the stimulus would increase compared to their frequency prior to the stimulation.
(c) The frequency of the spontaneous IPSPs would not change immediately after the stimulus compared to the frequency of spontaneous IPSPs prior to the stimulation.
(d) The amplitude of the spontaneous IPSPs would increase immediately after the stimulus, compared to their amplitude prior to the stimulation.
(e) The amplitude of the spontaneous IPSPs would decrease immediately after the stimulus, compared to their amplitude prior to the stimulation.

Question 24

The Morris water maze has been used to test learning and memory in rodents. In
(a) and
(b) there is a hidden platform (the large dot) and the rat learns where the platform is located. In
(c) and
(d) the platform has been removed and the rat must remember where the platform was located (its location prior to removal is indicated by the large dot). Which responses would be similar to a mouse in which CREB was selectively blocked in hippocampal CA1 neurons?

Question 25

The neural circuitry underlying the gill-withdrawal reflex is known: A sensory neuron in the gill synapses onto a motor neuron that innervates the gill. What is a neural mechanism for habituation?
(a) With repeated stimulation, the sensory neuron produces fewer and fewer action potentials.
(b) With repeated stimulation, the sensory neuron produces action potentials of decreased amplitude.
(c) With repeated stimulation the synaptic response in the motor neuron decreases.
(d) With repeated stimulation the motor neuron releases less neurotransmitter.
(e) With repeated stimulation the muscles become fatigued.

Question 26

For the left graph, rats were given a shock when they were placed in a specific environment. After they associated the shock with the environment, their hippocampus was removed at different intervals (7, 14, and 28 days after training). What happened to the rats with hippocampal lesions, compared to controls?
(a) The rats with hippocampal lesions learned the task faster.
(b) The longer the investigators waited after training to lesion the hippocampus, the less the lesion effected fear memory.
(c) The longer the investigators waited after training to lesion the hippocampus, the more of the task the rats forgot.
(d) The rats that had hippocampal lesions 1 and 7 days after training were much more fearful, and therefore had a stronger association between the US and the CS, than control rats.
(e) The control rats forgot the task, whereas rats with hippocampal lesions had better long-term memory.

Question 27

In 2000, Eric Kandel received the Nobel Prize in Physiology and Medicine, along with two other people for their "discoveries concerning signal transduction in the nervous system." Most of Kandel's work uncovered the contributions of the cAMP signal transduction pathway in memory formation in Aplysia. Why are the discoveries in Aplysia so important for our molecular understanding of learning and memory?
Where Does Learning Occur, and Where Is Memory Stored in the Brain?

Question 28

Hebb's postulate from 1949 states "When an axon of cell A is near enough to excite cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased." Give an example of how synaptic plasticity results in:
A. Growth processes
B. Metabolic changes
What Is the Relationship Between Learning and Synaptic Plasticity?

Question 29

Figure Q10-21 demonstrates spike-timing dependent activity. Figure Q10-21
A. What is the approximate change in EPSC amplitude when the presynaptic input occurs 60 ms prior to the postsynaptic action potential?
B. What is the approximate change in EPSC amplitude when the presynaptic input occurs 10 ms before the postsynaptic action potential?

Question 30

The hippocampus is not essential for long-term memory storage. Defend this statement with reference to the human patient H.M.
Questions 10-37, 10-38, 10-39, and 10-40 refer to Figure Q10-37. Figure Q10-37 shows evidence for neocortical contributions to long-term storage in explicit memory. Figure Q10-37

Question 31

What was one of the conclusions from this experiment?
(a) Learning does not require the hippocampus.
(b) The hippocampus is necessary for long-term memory storage.
(c) The hippocampus is involved in fear memory.
(d) Fear memory become less dependent on the hippocampus over time.

Question 32

What are some of the challenges in linking correlation of changes in synaptic strength in the hippocampus to causations of learning and memory? Briefly describe one experiment that has provided a better link between correlation and causation.

Question 33

Figure Q10-29 shows short- and long-term memory in Aplysia using the gill withdrawal reflex. Figure Q10-29
A. What would happen to the 4 single shock response if cAMP was inhibited?
B. What would happen to the 4 single shock response if CREB was inhibited?
C. What would happen to the 4 days, 4 trains per day response if CREB was inhibited?

Question 34

Dopamine neurons in the VTA synapse onto neurons in the nucleus accumbens. Neurons in the VTA are dopaminergic and is has been hypothesized that dopaminergic neurons signal reward prediction error. In this hypothesis the actual reward is compared with the predicted reward. If these two things are not equal dopaminergic signals change the predicted reward so that it matches the actual reward. Figure Q10-42
A. Figure Q10-42 shows a recording from a VTA dopaminergic neuron in a monkey. What happened when only the juice was presented to the animal prior to training? Was the predicted reward similar to the actual value? Explain your answer.
B. After training of a light to predict the amount of juice, what happened to the response to juice and why?
C. The juice was then NOT given to the monkey after it was predicted by the light. What happened and what is the reason for this response based on the abstract circuit model?

Question 35

Aplysia display many forms of learning including habituation and sensitization. If the siphon is touched, the gill withdraws. How is habituation of this reflex generated?
(a) Tail shock in combination with a touch of the siphon
(b) Continual tactile stimulation of the siphon results in an increase in the gill withdrawal
(c) Continual tactile stimulation of the siphon results in a decrease in the gill withdrawal
(d) A single tactile stimulation of the siphon results in long-term changes in the gill withdrawal

Question 36

The advantage of working with Drosophila is that molecular pathways underlying synaptic plasticity and learning can be identified. When investigators screened for Drosophila with defects in learning and memory they found several, including dunce and rutabaga. What proteins do these genes encode?
(a) Adenlyate cyclase and phosphodiesterase
(b) cAMP and PKA
(c) Serotonin and cAMP
(d) Dopamine and the dopamine receptor
(e) Dopamine and PKA

Question 37

Assume we can record spatially related neural activity from the entorhinal cortex and hippocampus of human. You are on vacation in London and have a map to find the Tower of London (you also do not have a smartphone).
A. What spatially related activity would you see in the entorhinal cortex as you are walking around London with your map with Cartesian coordinates?
B. What activity pattern would you see in the hippocampus as you were moving toward your destination?
C. Once you arrived at the Tower of London you find you need to move to the gate that is in the neighboring wall and so you have to walk along one wall of a building. What activity pattern would you see in the entorhinal cortex?

Question 38

According to the circuit diagram in Figure Q10-41, why does lesioning the amygdala disrupt contextual and fear conditioning whereas hippocampal lesions only disrupt contextual conditioning? Figure Q10-41

Question 39

Figure Q10-31 shows the circuitry and molecular cascade underlying olfactory learning in Drosophila. The CS is the odor and the US is the shock. Figure Q10-31
A. Why does the US paired with the CS result in olfactory conditioning?
B. Why would a different odorant not result in olfactory conditioning?
C. How could you test whether increases in the cAMP pathway in the mushroom body neurons contribute to olfactory conditioning?
D. Based on what is shown in Aplysia, what molecular pathway could contribute to long-term memory formation?

Question 40

Early experiences can shape neuronal circuitry and long-term memory. One example of this is the development of the auditory map in owls. Young owls were fitted with goggles that shifted their visual world. When the synaptic terminals of ICC to ICX were examined, owls raised with prisms had substantially expanded projections compared to owls raised without prisms. Based on this long-lasting change in neuronal connectivity, what do you think would happen if prisms were put back onto an adult owl that was initially reared with the prisms?
(a) The adult owl would not be able match the auditory and visual target because there would be a mismatch between the auditory terminals and visual terminals in the tectum since this was set up incorrectly when the bird was a juvenile.
(b) The adult owl would not be able to match auditory and visual terminals because the auditory input and the visual input would have been re-segregated and there would no longer be overlap.
(c) The adult owl would be able to relearn and match auditory input to the shifted visual input due to a regrowth of those synapses.
(d) The adult owl would be able to relearn and match auditory input to the shifted visual input because the connections are maintained.
Answers