BMS248 Lecture 10/11 - LTP + LTD

Question 1

What is a Hebbian synapse?

Answer 1

A synapse that increases in effectiveness/strength because of simultaneous activity in pre and postsynaptic neurons

Question 2

What area of the brain is primarily involved in memory formation? (particularly spatial)

Answer 2

The hippocampus

Question 3

What is the pathway of the hippocampal circuit?

Answer 3

. Entorhinal cortex to Dentate gyrus - via perforant pathway
2. Dentate gyrus to CA3 - via Mossy fibres
3. CA3 to CA1 - via Schaffer collaterals
4. Output via Fornix + Subiculum

Question 4

What is the pathway of the hippocampal circuit?

Answer 4

1. Entorhinal cortex to Dentate gyrus - via perforant pathway
2. Dentate gyrus to CA3 - via Mossy fibres
3. CA3 to CA1 - via Schaffer collaterals
4. Output via Fornix + Subiculum

Question 5

What is LTP?

Answer 5

Persistent strengthening of synapses that leads to long-lasting increase in signal transmission between neurons - via high frequency stimulus
INCREASE IN EPSP

Question 5

What is LTP?

Answer 5

Persistent strengthening of synapses that leads to long-lasting increase in signal transmission between neurons - via high frequency stimulus
INCREASE IN EPSP

Question 6

Where does LTP occur? What kind of synapse is this?

Answer 6

CA3 to CA1 synapses - via Schaffer collaterals
Glutamatergic synapse

Question 7

How does LTP show input specificity?

Answer 7

Restricted to activated synapses rather than all the synapses on a given neuron

Question 8

How does LTP show co-incidence?

Answer 8

Two pathways converging on the same target can both be strengthened if they fire together (greater EPSP) - does not require HFS

Question 9

What are the 3 types of glutamate receptors?

Answer 9

1. NMDAR - increase in Ca2+ at postsynaptic neuron
2. AMPAR - depolarises postsynaptic neuron (Na+ and K+)
3. mGluR - GPCR

Question 10

Co-operativity is a result of what kind of block on NMDA receptors and how?

Answer 10

Voltage dependent Mg2+ block - the receptor needs to be indirectly pre-activated by a separate depolarising input (requires glutamate and depolarisation)

Question 11

Co-operativity is a result of what kind of block on NMDA receptors and how?

Answer 11

Voltage dependent Mg2+ block - the receptor needs to be indirectly pre-activated by a separate depolarising input (requires glutamate and depolarisation)

Question 12

What is activated in early phase LTP by NMDAR (induction)?

Answer 12

1. NMDAR allows influx of Ca2+
2. This activates CaMKII (calmodulin kinase II)
3. Autophosphorylation of CaMKII - goes on to phosphorylate other proteins
4. Constant activation triggered by Ca2+ during LTP

Question 13

Phosphorylation by CaMKII enhances what and how?

Answer 13

AMPA currents - amplitude of current increases (greater EPSP) - this occurs by AMPAfication (greater no of AMPA receptors delivered to the postsynaptic neuron)

Question 14

What is the result of late phase LTP (expression)?

Answer 14

Change in gene expression and therefore the protein synthesis - takes effect 1hr after initiation

Question 15

What signalling is responsible for late phase LTP?

Answer 15

cAMP signalling

Question 16

How does the change in gene expression in late phase LTP occur?

Answer 16

1. cAMP activates PKA - which translocates to nucleus
2. In the nucleus it phosphorylates CREB complex
3. This replaces inactive CREB-2, with active phosphorylated CREB-1
4. Leading to the initiation of transcription by CRE transcription factor

Question 17

What kind of proteins are produced by late phase LTP?

Answer 17

Channels/proteins that translocate to the PSD - this increases amplitude of EPSP

Question 18

Knockout/mutation of CaMKII, NMDARs, cAMP pathway have what effect?

Answer 18

Effect aspects of learning/memory - LTP is only necessary but not sufficient for some memory formation

Question 19

What is the Cerebellar LTD circuitry and how does LTD occur?

Answer 19

• Paired climbing fibre and parallel fibre onto a single Purkinje cell
• Stimulate both at same time: get a decrease in EPSP - requires co-incidence
• This is input specific (like in LTD)

Question 20

What receptors do climbing fibres and parallel fibres possess?

Answer 20

• Climbing fibres use AMPAR
• Parallel fibres use AMPAR + mGluR

Question 21

What is the mechanism of Cerebellar LTD?

Answer 21

1. Ca2+ entry leads to activation of PKC
2. This phosphorylates GluR2 subunit (different to LTP) of AMPA receptors on parallel fibre
3. Leads to a decrease in the number of receptors by endocytosis - internalisation
4. Reduced current - reduced EPSP

Question 22

Inhibitors of what prevent LTD?

Answer 22

Endocytosis

Question 23

Where does LTD take place in the Hippocampus?

Answer 23

CA3 to CA1 synapse with low frequency stimulation (LTP - high frequency)

Question 24

What is depotentiation?

Answer 24

Reversal of a previous LTP

Question 25

What is depotentiation?

Answer 25

Reversal of a previous LTP

Question 26

The amount of what receptor activation determines the probability of inducing LTP or LTD, and why?

Answer 26

The amount of NMDA receptor activation:
LTP - HFS - high receptor activation
LTD - LFS - low receptor activation

Question 27

What is the mechanism of Hippocampal LTD?

Answer 27

1. Low frequency stimulation
2. Low levels of NMDAR
3. Low levels of CA2+
4. Phosphatase activation (rather than kinase in LTP)
5. Reduction in AMPAR efficacy
6. Less current - reduction in EPSP