L7: Cellular Mechanisms of Learning & Memory

Question 1

There are 2 types of memory: declarative & non-declarative. Compare them.

Answer 1

Declarative memory: available to consciousness; have to think about (e.g. phone #s, past events)P

Non-declarative memory (aka procedural memory): automatic (e.g. how to ride a bike, how to use a phone)

Question 2

Patient H.M had b/l resection of much of his hippocampus & medial temporal lobe for his intractable epilepsy. What happened post-resection?

Answer 2

• H.M had anterograde memory loss
• intact retrograde memory
• normal IQ
• normal short-term (working) memory
• intact non-declarative memory

therefore, hippocampus plays a vital role in forming declarative memory

Question 3

Define immediate, working and long-term memory

Answer 3

Immediate memory = within seconds

Short-term memory aka working memory = ability to hold & manipulate information; limited in duration & capacity

Long-term memory aka Engram = depends on changes in efficiency of synaptic transmission (strengthen synapses will lead to better long-term memory storage = long-term potentiation)

Question 4

Intrinsic Tri-synaptic Circuitry: what is it and what are the 3 sets of synapses found here?

Answer 4

it is a relay of synaptic transmission in hippocampus that if under right stimulation can generate long term potentiation which is the strengthening of synapses helping with the storage of long-term memory

3 sets of synapses:
1 - granule cells (excitatory input cells)
2 - CA3 pyramidal neurons
3 - CA1 pyramidal cells

Question 5

Long term potentiation (LTP) is a long-lasting increase in synaptic strength. What is the role of NMDA receptor and AMDA receptor activation on LTP?

Answer 5

• NMDA receptor activation (also requires glycine, Ca2+) is REQUIRED in LTP so needed for induction of LTP
• AMDA receptor activation is needed for maintenance of LTP

Question 6

What does LTP do to synapses?

Answer 6

strengthens synapses by causing changes in shape of synaptic spines & add more synaptic spines increasing surface area of dendrites so neurons can receive more information

Question 7

Explain the 2 properties of specificity and associativity of LTP

Answer 7

1) Specificity
- LTP is input specific
- restricted to activated synapses
- selective storage of information at synapses

2) Associativity
- associations are made when remembering things
- weak stimulation of a pathway occurs when a neighboring pathway is strongly activated, both synaptic pathways will undergo LTP

Question 8

In maintaining LTP, AMPA receptors are activated. What causes the increase in insertions of AMPA receptors on post-synaptic membranes?

Answer 8

Ca2+ release (via metabotropic glutamate receptor activation) starts a series of rxns that lead to increase insertions of AMPA receptors on post-synaptic membranes which will lead to increase EPSPs

Question 9

How many phases are associated with LTP?

Answer 9

2 phases that are DEPENDENT on Ca2+
1-short-term (early phase) = maintenance of LTP, active kinase activity , INDEPENDENT of protein synthesis
2- long-term (late phase) = natural extension of early phase; more spines growing, involves protein synthesis & gene transcription

Question 10

How important is protein synthesis in maintaining LTP?

Answer 10

LTP involves 2 phases that are dependent on Ca2+. The long-term phase involves protein synthesis. It is shown that when given a protein synthesis inhibitor (e.g. anisomycin), LTP will decay within a few hrs proving that protein synthesis is impt in maintaining LTP

Question 11

What is Long-term depression (LTD)?

Answer 11

long-lasting decrease in synaptic strength

Question 12

Why is LTD necessary?

Answer 12

b/f if synapses only undergo LTP, eventually would reach maximal efficiency, making it difficult to encode new info. Therefore, LTD and LTP have polarizing effects on one another (LTD can erase LTP, vice versa)

Question 13

Explain the mechanism involved in LTD

Answer 13

• increase Ca2+, but small and slow rises
• NMDA receptor activation but not as robust as LTP
• will activate phosphatases (as opposed to kinases in LTD)
• internalization of AMPA receptors = decrease AMPA receptors (as opposed to LTP in which AMPA receptors are increased in post-synaptic membrane)
• decrease in synaptic strength (as opposed to increased in strength in LTP)

Question 14

When can you observe LTD?

Answer 14

When synapses are stimulated at a LOW RATE for LONG PERIODS (10-15 min)

Question 15

Where are long-term memories stored?

Answer 15

hippocampus is involved in acquriing and storing declarative memory and also involved in transferring this memory to cortical structures for consoldiation/long-term storage

Question 16

What are some limitations of working memory/short-term memory?

Answer 16

capacity & duration

Question 17

Since both AMPA and NMDA receptor activations are required for LTP, explain what type of frequency & intensity stimulus are needed to activate these receptors.

Answer 17

low-frequency, low-intensity stimulus will only activate AMPA receptors b/c they are always firing

-NMDA receptors are activated by high intensity, high frequency stimulus

Question 18

What happens when you inject NMDA receptor antagonist before the high intensity high frequency stimulus? What about after?

Answer 18

using the schaffer collateral-CA1 synapses to study LTP, if one injects NMDA receptor antagonist before the high intensity high frequencey stimulus, one will not see LTP b/c NMDA receptor activation is REQUIRED for INDUCTION of LTP. If the antagonist is added to the synapses during the high intensity high frequency stimulus, LTP is still observed b/c NMDA receptor was activated before the antagonist was given.

Question 19

LTP requires gene transcription and protein translation, including proteins associated with synaptic growth. Which enzyme plays a role?

Answer 19

kinases diffuse to CA1 cell nuclei to influence genes that trigger long-lasting post-synaptic modifications