7. Learning and Memory: LTP & LTD Flashcards
what is working memory dependent on
persistent neural activity
how do we know that working memory is dependent on persistent neural activity
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
how do prefrontal cortex neurons persistently fire
calcium channels are inserted into the membrane to allow depolarisation
what is long term memory dependent on
long-lasting changes in the strength of synaptic connections
what does HFS stand for
high frequency stimulation
describe how excitatory field responses can be used to measure LTP
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
what blocks NMDA receptors
Mg2+
NMDa receptors are coincidence detectors, what does this mean
they must have glutamate bound and the post-synaptic membrane must be depolarised (Mg2+ block removed)
describe the process of NMDA receptor dependent LTP
- high presynaptic activity induced by HFS = depolarisation of the post-synaptic dendrite
- Mg2+ block on NMDA receptor is released = Ca2+ influx
- Ca2+ stimulates intracellular signalling cascade that activates CREB signalling
- CREB signalling promotes retrograde signalling molecules that enhance neurotransmitter release in the presynaptic membrane
- 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.
name 2 retrograde signalling molecules
nitric oxide
arachidonic acid
what stimulates CREB signalling
protein kinase C
tyrosine kinase
describe evidence proving a role of NMDA receptors in learning
NMDA receptor antagonists of the dentate gyrus impaired learning of the spatial water maze
what happens to KO mice with no NMDA receptor in the CA1 subfield
memory and LTP is impaired
what are the two phases of LTP
early and late LTP
what is the difference between early and late LTP
early LTP does not require any protein synthesis, cAMP or PKA activation
late LTP involves gene transcription via the CREB pathway
what is long term depression
the mechanism by which the brain attenuates synaptic efficacy
describe the mechanism of LTD
- low frequency stimulation produces modest post-synaptic depolarisation
- release of NMDA-r Mg2+ is less effective
- less calcium enters the post-synaptic neuron
- CAMKII is not activated
- Calcineurin is activated
- phosphatase activated and AMPA is removed from the membrane
- the excitatory post-synaptic potential is reduced
what is LTD’s hypothesised behavioural relevance
mice with selectively impaired LTD and not LTP fail to learn a new location in the Morris water maze = spatial memory role
where are new neurons synthesised
in the dentate gyrus
where is the dentate gyrus found
in the hippocampus
what are new neurons sensitive to
LTP
what happens to mice who have genetic ablation of neurogenesis
impaired performance of the Morris water maze
what is deficient hippocampal neurogenesis implicated in
defective learning and memory
what is the process of memory consolidation
a process by which temporary fragile memory is transformed into more stable, long-lasting memory
where are new memories stored
hippocampus
where are consolidated memories stored
in the neocortex
describe the novel object recognition task
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
what have mice studies using the novel object recognition task found to play a role in memory consolidation
CaV1.2
- a voltage gated calcium channel - hypo function of this channel prevents object recognition at 24 hours - suggesting deficits in memory consolidation.
