L10 - LTP and LDP mechanisms Flashcards
what did Donald Hebb state
coordinated activity of a presynaptic terminal and a postsynaptic neuron strengthen the synaptic connections between them
what does Alzheimer’s target early
the hippocampus - inability of patients to acquire new memory
what is the hippocampus responsible for
spatial memory information
outline the simplified hippocampal circuitry
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
what is LTP
persistent increase in synaptic strength following high frequency stimulation of a chemical synapse - increase in EPSP amplitude
how to record an LTP
stimulate CA3 neuron, record from CA1 neuron - will get an EPSP
what does it mean by LTP shows input specificity
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
where is LTP localised
in the synapses between input and output
what is another way to trigger LTP
simultaneously stimulate input and output at the same time
how can two pathways converging on the same target be strengthened
if they fire together
state of NMDA receptor when the neuron is hyper polarised
Mg is bound close to the pore of the NMDA receptor preventing calcium influx
outline opening of NDMA receptor
- glutamate binds to the AMPA receptor allowing Na+ influx
- Na+ influx causes the neuron to depolarise
- Mg2+ block on the NMDA receptor is removed
- Calcium can now enter through the NMDA receptor
difference between early and late LTP
late LTP requires protein synthesis - signal that goes to nucleus that triggers the transcription of proteins
outline early LTP
- activation of NMDA receptor - mediates calcium entry
- activates calmodulin kinase 2
- can phosphorylate a lot of proteins at once
- phosphorylation of AMPA receptor
what properties does calmodulin kinase 2 have
can phosphorylate a lot of proteins at once
autophosphorylation (stabilises in an open configuration)
what are the 2 subunits of calmodulin kinase 2
catalytic and regulatory subunits
the regulatory covers the catalytic preventing it from phosphorylating other proteins
what is AMPAfication
the delivery of readily prepared AMPA receptors to the synapse
outline late phase LTP
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
what is CRE
calcium responding element
what is LTD
long term depression - decrease in sensitivity to a neurotransmitter, can be related to plasticity and help brain to memorise
morphology of a purkinje cell
huge dendritic tree, large and dense, only in one plane, 10s of thousands of synapses
what is a climbing fibre
grows around purkinje cell and forms synapses with that purkinje cell
how many synapses are made between a parallel fibre and a purkinje cell
1
what does stimulation of the climbing fibre cause
massive depolarisation of the purkinje cell (EPSP)
what does stimulation of the parallel fibre cause
small depolarisation
what happens if stimulate both the climbing fibre and the parallel fibre
get a decrease in the EPSP amplitude
what are the 2 types of LTD
depotentiation - happens after the removal of previous potentiation
LTD de novo. - happens with no previous potentiation (most likely to be involved with memory)
outline the general mechanisms for LTD induction
generally requires NMDA receptors
often evoked by LFS
often requires calcium influx and activation of different phosphates
often involves glutamate or serotonin and endocanabinoids
do cerebellar LTD mechanisms involved NMDA receptors
No
outline cerebellar LTD mechanisms
- stimulate climbing fibre, causing stimulation of AMPA receptor
- leads to membrane depolarisation
- activates voltage gated calcium channels
- calcium influx
- activates protein kinase A
- stimulate parallel fibre, stimulates metabotropic glutamate receptors
- activates enzyme called phospholipase-C
- stimulates lipid DAG
- DAG activates protein kinase C
get reduction of AMPA currents
what is the function of PKC
phosphorylates AMPA. receptor subunit GluR2, reduces AMPA currents by endocytosis
where does LTD occur
at the CA3-CA1 synapse with LFS (1-5Hz)
what does the degree of NMDA receptor activation dicate
the probability of inducing LTD or LTP
what happens if only stimulate NMDA a small amount
get LTD
what happens if stimulate NMDA a large amount
get LTP
