Long Term Potentitation

Question 1

What is memory?

Answer 1

Retention and storage of learned knowledge. (Stored in different areas throughout brain).

Question 2

What brain regions does LTP occur in?

Answer 2

Many - striatum, VTA, spinal cord…but mostly studied in the hippocampus due to its monosynaptic pathways.

Question 3

Explain how LTP is studied in vitro?

Answer 3

Rat hippocampal slices of CA1 regions following stimulation of CA3 schaffer collaterals.

400-500 micrometer thick slice - bathed in artificial CSF.

Question 4

Explain the EPSP recordings following a single stimulation, followed by high frequency repeated stimuli, followed by 1 stimulation.

Answer 4

1 stimulation - normal EPSP.
1-4 trains of 5-10 stimuli - tetanus.
1 stimulation - larger EPSP for same stimulation after tetanic stimulation.

Question 5

Define LTP.

Answer 5

Long lasting enhancement of synaptic response.

Question 6

Explain transmission at the glutaminergic CA3:CA1 synapse before LTP.

Answer 6

Glutamate is released.
Acts on AMPA receptors - Na+ in, K+ out. EPSP.
Can’t act on NMDA - Mg++ block.
Acts on mGluR - Gq linked which activated PKC.

Question 7

Explain the molecular basis for LTP induction.

Answer 7

1) Increase Can++ dependant exocytosis of glutamate.
2) Increase AMPA-R activation = increased depolarisation
3) Increase mGlurR activation - PKA mediated phosphorylation of NMDA-R to increase sensitivity of NMDA-R to glutamate.
4) Removal of Mg++ block - ca++ entry through NMDA-R
5) Activation of VOCC
6) Increase intracellular calcium,
7) Ca__ dependant production of retrograde messgender (NO…act presynaptically to increase glut release).
8) Activation of Ca++ dependant enxymes/gene transcription - which underlies the later phase of LTP expression.

Question 8

Explain the molecular basis of LTP induction.

Answer 8

1) Increase in Ca++ intracellularly…
…PLA2, AA, activation of PKC and Ca++?CamKinase…increase sensitivity of AMPA receptors…
Persitant increase in EPSP.

1)Increase in Ca++ intracellularly…gene transcription and new protein synthesis…
…increase AMPA receptor densitity…increase EPSP.

or…
increase Ca++ intracellularly leads to neurotrophic factor production…neural sprouting and increased current spread,..increased EPSP.