synaptic plasticity 1 Flashcards
what is plasticity?
relates to the idea that the nervous system is constantly modifiable
this is how we adapt to our changning environment, learn, develop skills and store information
how can plasticity occur?
physiologically due to acitivity or due to injury/disease/addiction
functional cortical plasticty
motor training (e.g in pianists) changes the motor homonuclus in areas associated with fingers and hands
injury dependent cortical plasticity
e.g finger amputation
homoculus changes for removed digits, those regions that were previously represented by digits is taken over by the other fingers and their cortical territories largens
types of neuroplasticity
- enhancement of existing connections
- formation of new connections
examples of enhacement of existing connections
a. synapse development
b. synapse strengthening
examples of formation of new connections
a. unmasking
b. sprouting
duration of enhancement of existing connections
ms-1 to hours to days
duration of formation of new connections
minutes to days to months
what can change in the brain to bring about plasticity?
action potentials (all or nothing so cant change size but can change frequency)
synaptic transmission
why do we use the hippocampus to study learning and memory?
it has an identified role (spatial learning in rodents and humans)
has a simple neuronal structure
what is hebb’s postulate?
neurons that fire together wire together
the hippocampal network
- input from entorhinal cortex that forms connections with the dentate gyrus and CA3 pyramidal neurosn via the perfornat path
- CA3 neurons also receive input from the DG via mossy fibres
- they send axons to CA1 pyramidal cells via the schaffer collateral pathway as well as to CA1 cells in the contralateral hippocampus via the associational commissural pathway
- CA1 neurons also receive input directly from the perforant path and send axons to the subiculum
- these neurons send the main hippocampal back to the entorhinal cortex forming a loop
what is long-term potentiation?
strength of synaptic connections between neurons is increased following repeated or persistent stimulation
bliss and lomo 1973
put recording electrode on dentate gyrus of rabbits
stimulation of axons at a low basal rate (one stimulus per 15 seconds) produced a stable synaptic response in the EPSP
single high frequency train resulted in persistent increase in response size- LTP
basic properties of hippocampal LTP
- long-lasting
- input specificity
- cooperativity
- associativity
input specificity in hippocampal LTP
only synapses that are active during stimulation will be strengthened
meaning: Ii you stimulate synapse A on a neuron, but not synapse B, only synapse A will undergo LTP
cooperativity and hippocampal LTP
multiple weak inputs must be activated together to produce enough depolarization to trigger LTP
meaning: a single weak input might not be enough, but if several synapses fire together, their combined effect can induce LTP
associativity and hippocampal LTP
a weak input can undergo LTP if it’s active at the same time as a strong input nearby
meaning: the strong input provides enough depolarisation to help the weak input’s NMDA receptors open — both synapses get potentiated
other properties of hippocampal LTP
- can be reversed
- can be saturated (cant continually produce potentiation)
mechanisms of hippocampal LTP
- strong postsynaptic depolarisation
- presynaptic glutamate release
- leads to activation of AMPA receptors, allowing Na⁺ in
- Mg²⁺ is expelled from the NMDA receptor channel, NMDA receptors now open, allowing Ca²⁺ to enter the postsynaptic cell
- calcium influx is the key trigger for LTP
APV and LTP
APV is an NMDA receptor antagonist so blocks LTP but there is still glutamate transmission
what does low frequency stimulation (LSF) induce at schaffer collaterals?
long-term depression
how to induce LTD at CA3-CA1 synapse?
- LFS results in prolonged low-level Ca²⁺ entry via NMDARs
- activate phosphatases that dephosphorylate AMPARs
- endocytosis of AMPAR
- reduced synaptic responsiveness to glutamate
- can be saturated and reversed
- has different mechanisms (e.g mGluRs, VGCC, KARs)
what is synaptic silencing?
endocytosis of AMPA receptors=decrease therefore prune synapses
how can LTP and LTD both be dependent on NMDA activation?
- size and time course of NMDA and calcium influx differ between LTP and LTD
- LTP results from large intracellular calcium rise for short period of time
- LTD results from smaller rise in calcium over longer time
- enzymes (kinases/phosphateses) have different sensitivities to calcium
LTP, hebbian plasticity and NMDA receptors
syanpses strengthened when both postsynaptic and presynaptic cell are active during induction protocol
NMDA receptor acts as a coincident detector- needs postsynaptic depolarisation and presynaptic release of glutamate
is LTD anti-hebbian?
syanpses are weakened when both the pre and post synaptic cells are active during induction protocol
LTD in other brain regions:
cerebellum for motor learning
perihinal cortex for object recognition
cerebellar LTD
if you stimulate parallel fibres couples with depolarisation of purkinje cells you get LTD
mechanisms of cerebellar LTD
- requires activation of AMPA and metabotropic glutamate
- activation of protein kinase C
- AMPA internalised (endocytosis) so reduces at cell surface
perihinal LTD
- LFS cause modest intracellular calcium
- activate NMDAR
- activate mGluR1/5
- AMPA internalisation
how can you block LTD?
LTD can be blocked by
putting a peptide into the postsynaptic cell that interferes with removal of AMPA receptors from the
cell surface
synaptic plasticity and alzheimers
problems with memory
LTP in the hippocampus may be reduced
synaptic plasticity and parkinsons
loss of LTD in striatum
syanptic plasticity and schizophrenia
reduction of NMDA receptor functiom
