Molecular Basis of Memory

Question 1

What is “Hebb’s Rule”?

Answer 1

If 2 neurones are excited at the same time, then the active synapse between them is strengthened

Question 2

Name the major site of episodic memory

Answer 2

Hippocampus

Question 3

What widely used model mediates associative memory?

Answer 3

Glutamate at the NMDA receptor

NB: this model requires protein synthesis

Question 4

What particular region of the brain is essential for long term memory?

Answer 4

CA1 region of the hippocampus- this is the primary model used in LTP

Question 5

What is long term potentiation?

Answer 5

Brief periods during learning where there is a long lasting increase in synaptic strength (greater excitatory post-synaptic current AND increase in synaptic transmission efficiency)

Question 6

Describe the changes in the intracellular calcium concentration initiated by NMDA?

Answer 6

Normal intracellular calcium is at 70nM

[after NMDA-r activation] -> >10uM

Question 7

What is the outcome of increased intracellular calcium?

Answer 7

Calcium binds to calmodulin and activates calc-dependent enzymes:

• CaMKII ]- important
• phosphodiesterase-1
• calcineurin
• nNOS
• adenylcyclase

Question 8

Describe the mechanism of of CaMKII’s activation

Answer 8

Calmodulin causes CaMKII to open, exposing threonine 286

Thre286 is phosphorylated -> CaMKII activation

Question 9

Where is CaMKII located?

Answer 9

Normally in the cytosol (along w/ a phosphatase)

After it is autophosphorylated, it moves to sub-synaptic region (until dephosphorylated by a protein phosphatase)

Question 10

Describe CaMKII’s action after auto-phosphorylation

Answer 10

Phosphorylates NMDA (via NR2B) and AMPA (via GluR1)

Question 11

Outcome of AMPA phosphorylation?

Answer 11

Becomes high-conductance AMPA-r (25pS)

Question 12

What 2 processes mediate enhanced AMPA-r function?

Answer 12

• increased single channel conductance

- increased AMPA receptor number at the synapse

Question 13

Describe properties of LTP-silent synapses

Answer 13

Spines only contain NMDA receptors, NOT AMPA

Question 14

How can LTP-silent receptors become able to support LTP?

Answer 14

LTP induces Ca2+, which triggers AMPA-r trafficking to silent synapses

Question 15

How are extracellular AMPA-rs recruited to LTP silent synapses?

Answer 15

AMPA-r auxillary protein: stargazin, recruits extracellular AMPA (GlurR1).

When stargazin is phosphorylated w/ CaMKII, it interacts w/ PSD95 (post-syn density protein), facillitating integration at synapse

Question 16

How are changes in synaptic strength consolidated?

Answer 16

CaMKIV activates transcription, which phosphorylates CREB

Question 17

How is CREB activated?

Answer 17

Phosphorylated by CaMKIV and PKA