LTP and LTD Flashcards
What is LTP
long term potentiation - the change in sensitivity in a neurone
name a location where LTP is often studies
at CA3 -CA1 hippocampal synapses
describe mechanism of LTP at CA3-CA1
at NMDA receptor
remove Mg2+ block by high fequency stimulus and the binding of glutamate
causes depolarisation and influx of Ca2+
what 2 ways does Calcium do to increase LTP in neurones
- stimulates kinas CaMK2 which phosphorylates AMPA receptors to increase their currents so stimultion of neuter more efficient
- stimulates kinase PKA so moves into nucleus, causes transcription that results in receptor being more sensitive to stimulus
what is the mechanism of LTD at purkinje synapses
if stimulate parallel and climbing fibres is causes decresase in the response of the cell
role of PKC in LTD in Hippocampus
activated by DAG and calcium, PKC phosphorylates AMPA to decrease its sensitivity
what determines if synapse in state of LTP or LTD
the concentration of calcium
describe an experiment that was used to test LTP and LTD
monkeys brought up in different environments
some with little stimulation (toys) some with lots
the more enriched the environment the more spines on the dendrites and more synapses
what is hebbians synapse
stimulate 1 neurone, causes EPSP in next neurone
hippocampus what is role ?
spatial memory formation and initiates storage
the hippocampus circuit
Entorhinal to dentate (perforant)
Dentate to CA3 (mossy fibres)
CA3 to CA1 (Schaffer collaterals)
Output via fornix and subiculum
what happens if you stimulate CA3
EPSP IN POSTSYNAPTIC CA1
if stimulate CA3 with high frequency stimulus what does it do
increase amplitude of EPSP and cause LTP (long term potentiation)
how does LTP occur
initiated when postsynaptic neurons become depolarized, NMDA receptor channels are activated, and Ca2 + flows into the postsynaptic neuron
One way to induce LTP is to use high-frequency stimulation to release large amounts of neurotransmitter to depolarize the postsynaptic cell.
structure role of NMDA receptors
NMDA receptors have a voltage-dependent Mg2+ block.
need to be indirectly pre-activated by a separate depolar
difference between early and late LTP
Early LTP is associated with short-term memory and late LTP with long-term memory
late requires protein synthesis
difference between spatial and temporal summation
Spatial summation occurs when multiple presynaptic neurones together release enough neurotransmitter (e.g. acetylcholine) to exceed the threshold of the postsynaptic neurone.
temporal summation occurs when one presynaptic neurone releases neurotransmitter many times over a period of time.
what enhances AMPA currents
Phosphorylation enhances AMPA currents.
role of cAMP in LTP
triggers the expression of genes as binds to CREB1
what mutations all affect aspects of learning
Mutations of CaMKII, NMDARs, cAMP
Drugs to enhance memor
Drugs to enhance memory (nootropics) also enhance LTP
AMPAkines - Alzheimer’s – poor success.
There are two main types of LTD
Depotentiation- Removal of previous potentiation
LTD de novo- No previous potentiation
is LTD hebbian?
LTD may be Hebbian (homosynaptic – like LTP) or non-Hebbian (heterosynaptic – not requiring pre-synaptic activity)
what does an LTD often require (but not always )
NMDA receptors
low frequency stimulation (LFS)
Ca2+ influx
activation of serine / threonine phosphatases
glutamate, but also diffuse transmitters e.g. 5-HT
what are the inputs and outputs of LTD circuitry
Inputs are +ve mossy and climbing fibres
Output (to DCN) are –ve Purkinje fibres
