L10 - LTP and LDP mechanisms

Question 1

what did Donald Hebb state

Answer 1

coordinated activity of a presynaptic terminal and a postsynaptic neuron strengthen the synaptic connections between them

Question 2

what does Alzheimer’s target early

Answer 2

the hippocampus - inability of patients to acquire new memory

Question 3

what is the hippocampus responsible for

Answer 3

spatial memory information

Question 4

outline the simplified hippocampal circuitry

Answer 4

main input is from the entorhinal complex to the dentate gyrus
synapse links dentate to CA3 neurons
Another synapse links CA3. to CA1 (Schaffer collaterals)
output via fornix and subiculum

Question 5

what is LTP

Answer 5

persistent increase in synaptic strength following high frequency stimulation of a chemical synapse - increase in EPSP amplitude

Question 6

how to record an LTP

Answer 6

stimulate CA3 neuron, record from CA1 neuron - will get an EPSP

Question 7

what does it mean by LTP shows input specificity

Answer 7

means that if have 2 different inputs to the same neuron and stimulate separately, can record EPSPs from each input. only the EPSP magnitude will change for the input stimulated

Question 8

where is LTP localised

Answer 8

in the synapses between input and output

Question 9

what is another way to trigger LTP

Answer 9

simultaneously stimulate input and output at the same time

Question 10

how can two pathways converging on the same target be strengthened

Answer 10

if they fire together

Question 11

state of NMDA receptor when the neuron is hyper polarised

Answer 11

Mg is bound close to the pore of the NMDA receptor preventing calcium influx

Question 12

outline opening of NDMA receptor

Answer 12

1. glutamate binds to the AMPA receptor allowing Na+ influx
2. Na+ influx causes the neuron to depolarise
3. Mg2+ block on the NMDA receptor is removed
4. Calcium can now enter through the NMDA receptor

Question 13

difference between early and late LTP

Answer 13

late LTP requires protein synthesis - signal that goes to nucleus that triggers the transcription of proteins

Question 14

outline early LTP

Answer 14

1. activation of NMDA receptor - mediates calcium entry
2. activates calmodulin kinase 2
3. can phosphorylate a lot of proteins at once
4. phosphorylation of AMPA receptor

Question 15

what properties does calmodulin kinase 2 have

Answer 15

can phosphorylate a lot of proteins at once

autophosphorylation (stabilises in an open configuration)

Question 16

what are the 2 subunits of calmodulin kinase 2

Answer 16

catalytic and regulatory subunits

the regulatory covers the catalytic preventing it from phosphorylating other proteins

Question 17

what is AMPAfication

Answer 17

the delivery of readily prepared AMPA receptors to the synapse

Question 18

outline late phase LTP

Answer 18

long term storage needs protein synthesis

• cAMP triggers expression of genes with CRE within the promotor
• CRE binds certain TFs (CREB-1 /CREB-2)
• during the LTP, CREB-2 is substituted by CREB-1. which is phosphorylated by protein kinase A causing transcription of certain genes

Question 19

what is CRE

Answer 19

calcium responding element

Question 20

what is LTD

Answer 20

long term depression - decrease in sensitivity to a neurotransmitter, can be related to plasticity and help brain to memorise

Question 21

morphology of a purkinje cell

Answer 21

huge dendritic tree, large and dense, only in one plane, 10s of thousands of synapses

Question 22

what is a climbing fibre

Answer 22

grows around purkinje cell and forms synapses with that purkinje cell

Question 23

how many synapses are made between a parallel fibre and a purkinje cell

Answer 23

1

Question 24

what does stimulation of the climbing fibre cause

Answer 24

massive depolarisation of the purkinje cell (EPSP)

Question 25

what does stimulation of the parallel fibre cause

Answer 25

small depolarisation

Question 26

what happens if stimulate both the climbing fibre and the parallel fibre

Answer 26

get a decrease in the EPSP amplitude

Question 27

what are the 2 types of LTD

Answer 27

depotentiation - happens after the removal of previous potentiation
LTD de novo. - happens with no previous potentiation (most likely to be involved with memory)

Question 28

outline the general mechanisms for LTD induction

Answer 28

generally requires NMDA receptors
often evoked by LFS
often requires calcium influx and activation of different phosphates
often involves glutamate or serotonin and endocanabinoids

Question 29

do cerebellar LTD mechanisms involved NMDA receptors

Answer 29

No

Question 30

outline cerebellar LTD mechanisms

Answer 30

1. stimulate climbing fibre, causing stimulation of AMPA receptor
2. leads to membrane depolarisation
3. activates voltage gated calcium channels
4. calcium influx
5. activates protein kinase A
6. stimulate parallel fibre, stimulates metabotropic glutamate receptors
7. activates enzyme called phospholipase-C
8. stimulates lipid DAG
9. DAG activates protein kinase C

get reduction of AMPA currents

Question 31

what is the function of PKC

Answer 31

phosphorylates AMPA. receptor subunit GluR2, reduces AMPA currents by endocytosis

Question 32

where does LTD occur

Answer 32

at the CA3-CA1 synapse with LFS (1-5Hz)

Question 33

what does the degree of NMDA receptor activation dicate

Answer 33

the probability of inducing LTD or LTP

Question 34

what happens if only stimulate NMDA a small amount

Answer 34

get LTD

Question 35

what happens if stimulate NMDA a large amount

Answer 35

get LTP