7. Learning and Memory: LTP & LTD

Question 1

what is working memory dependent on

Answer 1

persistent neural activity

Question 2

how do we know that working memory is dependent on persistent neural activity

Answer 2

primates performing the delayed match-to-sample visual working memory task were required to press a lever if they recognised the image for a reward

• found neurons in the prefrontal cortex persistently fire during the delay period

Question 3

how do prefrontal cortex neurons persistently fire

Answer 3

calcium channels are inserted into the membrane to allow depolarisation

Question 4

what is long term memory dependent on

Answer 4

long-lasting changes in the strength of synaptic connections

Question 5

what does HFS stand for

Answer 5

high frequency stimulation

Question 6

describe how excitatory field responses can be used to measure LTP

Answer 6

Schaffer collateral neurons are stimulated with HFS, we can record what happens to CA1 neurons in the hippocampal subfield (which is the post-synaptic cell)

if LTP has occurred, there should be a greater negative deflection in the excitatory field showing greater depolarisation 30 mins after HFS

Question 7

what blocks NMDA receptors

Answer 7

Mg2+

Question 8

NMDa receptors are coincidence detectors, what does this mean

Answer 8

they must have glutamate bound and the post-synaptic membrane must be depolarised (Mg2+ block removed)

Question 9

describe the process of NMDA receptor dependent LTP

Answer 9

1. high presynaptic activity induced by HFS = depolarisation of the post-synaptic dendrite
2. Mg2+ block on NMDA receptor is released = Ca2+ influx
3. Ca2+ stimulates intracellular signalling cascade that activates CREB signalling
4. CREB signalling promotes retrograde signalling molecules that enhance neurotransmitter release in the presynaptic membrane
5. CAMKII integrates more AMPA receptors into the membrane

synapse is strengthened = quantity of presynaptic neurotransmitter is increased and the post-synaptic membrane becomes more responsive.

Question 10

name 2 retrograde signalling molecules

Answer 10

nitric oxide
arachidonic acid

Question 11

what stimulates CREB signalling

Answer 11

protein kinase C
tyrosine kinase

Question 12

describe evidence proving a role of NMDA receptors in learning

Answer 12

NMDA receptor antagonists of the dentate gyrus impaired learning of the spatial water maze

Question 13

what happens to KO mice with no NMDA receptor in the CA1 subfield

Answer 13

memory and LTP is impaired

Question 14

what are the two phases of LTP

Answer 14

early and late LTP

Question 15

what is the difference between early and late LTP

Answer 15

early LTP does not require any protein synthesis, cAMP or PKA activation

late LTP involves gene transcription via the CREB pathway

Question 16

what is long term depression

Answer 16

the mechanism by which the brain attenuates synaptic efficacy

Question 17

describe the mechanism of LTD

Answer 17

1. low frequency stimulation produces modest post-synaptic depolarisation
2. release of NMDA-r Mg2+ is less effective
3. less calcium enters the post-synaptic neuron
4. CAMKII is not activated
5. Calcineurin is activated
6. phosphatase activated and AMPA is removed from the membrane
7. the excitatory post-synaptic potential is reduced

Question 18

what is LTD’s hypothesised behavioural relevance

Answer 18

mice with selectively impaired LTD and not LTP fail to learn a new location in the Morris water maze = spatial memory role

Question 19

where are new neurons synthesised

Answer 19

in the dentate gyrus

Question 20

where is the dentate gyrus found

Answer 20

in the hippocampus

Question 21

what are new neurons sensitive to

Answer 21

LTP

Question 22

what happens to mice who have genetic ablation of neurogenesis

Answer 22

impaired performance of the Morris water maze

Question 23

what is deficient hippocampal neurogenesis implicated in

Answer 23

defective learning and memory

Question 24

what is the process of memory consolidation

Answer 24

a process by which temporary fragile memory is transformed into more stable, long-lasting memory

Question 25

where are new memories stored

Answer 25

hippocampus

Question 26

where are consolidated memories stored

Answer 26

in the neocortex

Question 27

describe the novel object recognition task

Answer 27

mice show a preference for exploring novel objects in their environment. the more time spent with a novel object indicates that the mice have a memory of the familiar object

Question 28

what have mice studies using the novel object recognition task found to play a role in memory consolidation

Answer 28

CaV1.2
- a voltage gated calcium channel - hypo function of this channel prevents object recognition at 24 hours - suggesting deficits in memory consolidation.