BB30044: Synaptic Plasticity (RW)
o Synaptic plasticity is the ability of synapses to alter their
responsiveness. They can strengthen/weaken over time in response to
increases or decreases in their activity.
o Plasticity is thought to be a molecular determinant of memory and other
long-term plasticity changes in the brain.
o Involves 2 phenomena:
1. Large structural changes in synapses themselves
2. Alterations in receptor number/ subtypes
Plasticity and spine morphology:
o Morphological changes in dendritic spines are important in synaptic
plasticity
o There are distinct synaptic morphologies (e.g. filopodium, mushroom-
shaped, stubby, thin) that determine synaptic surface area, making the
synapse more/less able to transmit signals
Most common experimental models of synaptic plasticity:
o LTP (long term potentiation): enhanced, more responsive synaptic activity
o LTD (long term depression): reduced, less responsive synaptic activity
o Best characterised in the hippocampus – involved in the highest-order
forms of memory. Therefore these models can be extrapolated to models
of learning and memory – the concept that synapses have a ‘molecular
memory’, that signals received influences their response to subsequent
signals
o These long term changes in synaptic response can last up to several days
in vivo. However, LTP (as opposed to STP – short term potentiation) has
only been proved experimentally in rodent models, not humans.
Electrophysiology of LTP:
o The tetanic (repeated) stimulation of a synapse (train of action potentials)
creates robust activation
o After this stimulation, the synaptic response does not return to baseline –
it has a higher resting level. This is a potentiated synapse.
LTP in glutamatergic synapses:
o Plasticity is most studied in glutamatergic
synapses but not unique to them
o Initial stimulation: action potential
triggers presynaptic neurotransmitter
release from vesicles, and interaction
with postsynaptic receptors leads to a
postsynaptic Ca2+ influx and signal
transmission
o Repeated stimulation creates LTP:
potentiated synapse shows:-
1. A larger number of vesicles at the
nerve terminal so greater
, neurotransmitter release
2. More receptors expressed at the postsynaptic membrane
o Research points to a stronger influence of postsynaptic receptor changes
on plasticity, however both changes are likely to be important in different
contexts.
LTP vs LTD:
o In both cases, synaptic stimulation leads to a postsynaptic calcium influx.
Difference is in structural changes in the dendritic spine of the
postsynaptic neuron.
o LTP: calcium signalling shifts actin ratio in the spine towards more F-actin
(filamentous) than G-actin (globular). This enlarges the spine surface area
and increases synaptic responsiveness. As LTP progresses, there is
formation of new spines neighbouring existing spines, creating more
signalling potential.
o LTD: calcium signalling shifts actin ratio
in the spine towards more G-actin than
F-actin. This reduces spine surface area,
decreasing synaptic responsiveness. As
LTD progresses, spine pruning creates
areas of synaptic silence in the NS.
Key research q: can re-population of
dendritic spines be stimulated e.g. in
stroke, involving synaptic loss?
How does plasticity happen?
o Phosphorylation of glutamate receptors (NMDA and AMPA) to regulate
gating and currents
o Regulation of glutamate receptor trafficking and internalisation to alter
levels of cell surface expression
o Altering the probability of neurotransmitter release
o Signalling to transcription to influence expression of glutamate receptor
subunits and synthesise synaptic machinery (drives long-term changes
such as new spine generation)
LTP is coincidence dependent:
o Synaptic signal can only be potentiated if
the postsynaptic cell is depolarised (this
releases Mg2+ block on NMDAR to allow
Ca2+ influx)
o i.e. Potentiation does not occur if a signal
is received but the postsynaptic cell is
not depolarised, or if the postsynaptic
cell is depolarised but there is no signal
input.
o Due to NMDA receptor: acts as the coincidence detector – requires
glutamate release AND depolarisation in order to transmit signal
o Synaptic plasticity is the ability of synapses to alter their
responsiveness. They can strengthen/weaken over time in response to
increases or decreases in their activity.
o Plasticity is thought to be a molecular determinant of memory and other
long-term plasticity changes in the brain.
o Involves 2 phenomena:
1. Large structural changes in synapses themselves
2. Alterations in receptor number/ subtypes
Plasticity and spine morphology:
o Morphological changes in dendritic spines are important in synaptic
plasticity
o There are distinct synaptic morphologies (e.g. filopodium, mushroom-
shaped, stubby, thin) that determine synaptic surface area, making the
synapse more/less able to transmit signals
Most common experimental models of synaptic plasticity:
o LTP (long term potentiation): enhanced, more responsive synaptic activity
o LTD (long term depression): reduced, less responsive synaptic activity
o Best characterised in the hippocampus – involved in the highest-order
forms of memory. Therefore these models can be extrapolated to models
of learning and memory – the concept that synapses have a ‘molecular
memory’, that signals received influences their response to subsequent
signals
o These long term changes in synaptic response can last up to several days
in vivo. However, LTP (as opposed to STP – short term potentiation) has
only been proved experimentally in rodent models, not humans.
Electrophysiology of LTP:
o The tetanic (repeated) stimulation of a synapse (train of action potentials)
creates robust activation
o After this stimulation, the synaptic response does not return to baseline –
it has a higher resting level. This is a potentiated synapse.
LTP in glutamatergic synapses:
o Plasticity is most studied in glutamatergic
synapses but not unique to them
o Initial stimulation: action potential
triggers presynaptic neurotransmitter
release from vesicles, and interaction
with postsynaptic receptors leads to a
postsynaptic Ca2+ influx and signal
transmission
o Repeated stimulation creates LTP:
potentiated synapse shows:-
1. A larger number of vesicles at the
nerve terminal so greater
, neurotransmitter release
2. More receptors expressed at the postsynaptic membrane
o Research points to a stronger influence of postsynaptic receptor changes
on plasticity, however both changes are likely to be important in different
contexts.
LTP vs LTD:
o In both cases, synaptic stimulation leads to a postsynaptic calcium influx.
Difference is in structural changes in the dendritic spine of the
postsynaptic neuron.
o LTP: calcium signalling shifts actin ratio in the spine towards more F-actin
(filamentous) than G-actin (globular). This enlarges the spine surface area
and increases synaptic responsiveness. As LTP progresses, there is
formation of new spines neighbouring existing spines, creating more
signalling potential.
o LTD: calcium signalling shifts actin ratio
in the spine towards more G-actin than
F-actin. This reduces spine surface area,
decreasing synaptic responsiveness. As
LTD progresses, spine pruning creates
areas of synaptic silence in the NS.
Key research q: can re-population of
dendritic spines be stimulated e.g. in
stroke, involving synaptic loss?
How does plasticity happen?
o Phosphorylation of glutamate receptors (NMDA and AMPA) to regulate
gating and currents
o Regulation of glutamate receptor trafficking and internalisation to alter
levels of cell surface expression
o Altering the probability of neurotransmitter release
o Signalling to transcription to influence expression of glutamate receptor
subunits and synthesise synaptic machinery (drives long-term changes
such as new spine generation)
LTP is coincidence dependent:
o Synaptic signal can only be potentiated if
the postsynaptic cell is depolarised (this
releases Mg2+ block on NMDAR to allow
Ca2+ influx)
o i.e. Potentiation does not occur if a signal
is received but the postsynaptic cell is
not depolarised, or if the postsynaptic
cell is depolarised but there is no signal
input.
o Due to NMDA receptor: acts as the coincidence detector – requires
glutamate release AND depolarisation in order to transmit signal
