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Next to LTP, what is another imp mechanism of long-term plasticity?
Long-term depression
Where is LTD present?
At many glutamatergic synapses
What is LTD’s specificity?
LTD only happened when stimulated, repetitive stimulation at low frequencies elicits LTD → Bidirectional plasticity
What is the mechanism of LTD induction?
Induction of LTD dependent on either NMDA or meta glutamate receptors
Ca2+ influx in post-neuro, less than during LTP indictions
Protein phosphates activated
De-phorphorylation of AMPARs
What does the induction of both forms of LTD results show?
AMPARs removal from postsynaptic membranes
Decrese in condunctacce of individual AMPARs channels (low sodium ions diffusion)
Decreases in the size of spines and synaptic appositions of depressed synapses
Decreases in neurotransmitter release probability…mediated by endocannabinoids
What are the 2 sources for postsynaptic membrane depolarization?
Spatial or temporal summation of EPSPs generated at synapses onto same dendritic branch
Back-propagating action potentials: APs generated at axon initial segment can back- propagate into dendrite in many neurons due to presence of voltage-gated sodium channels in dendritic membrane
What is spike timing-dependent plasticity?
Timing of postsynaptic action potential relative to presynaptic action potential determines whether LTP or LTD is induced
How is LTP induced?
If the activation of the glutamatergic synapse closely precedes the backpropagating action potential
How is LTD induced?
If the activation of the glutamatergic synapse closely follows the backpropagating action potential
What does the magnitude of plasticity depend on?
Exact timing between synaptic activation and back propagating AP
When is the magnitude of the increase or decrease in ESPSs the largest?
If SA and BP coincide closely
Why is the cerebellum important?
For learning and remembering motor skills
What do the projection neurons in cerebellar cortex, Purkinje cells, have?
Convergent glutamatergic input
What does the coincident activation of parallel fibre synapses and climbing fibre leads to?
Long-term depression at parallel fibre synapses
What does the Parallel fiber LTD lead to?
Sustained alterations of output from cerebellar cortex: Thought to underlie motor learning
Parallel fiber LTD requires two signals, what are thy?
Climbing fiber activation leads to firing of Purkinje cell and influx of Ca2+ though channels
Activation of Gq-coupled metabotropic glutamate receptors at parallel fiber synapse leads to activation of PLC and Ca2+ release through IP3 receptors
Calcium burst leads to internalization of AMPARs
What is another form of longterm plasticity?
Homeostatic plasticity
What is “Runaway” potentiation?
Hebbian plasticity presents problem for stability of circuits
What is the need for homeostatic plasticity mechanism?
Ensures that activity level of postsynaptic neuron remains within a physiological range
What is synaptic scaling?
Mechanism of homeostatic plasticity that has been discovered
What does synaptic scaling lead to?
Downgrading oof the efficacy pf all afferent synapses on a neuron if the activity of said neuron is too high
What does synaptic scaling preserve?
Preserves relative distribution of synaptic weights
What is a second mechanism of homeostatic plasticity?
Metaplasticity
What is metaplasticity?
Metaplasticity occurs at glutamatergic synapses that can undergo NMDAR- dependent LTP and LTD
At synapses with bidirectional plasticity, the activity level of the postsynaptic neuron controls what?
Modification of threshold, or requirements for LTP and LTD induction
What happened if postsynaptic neuron is highly active?
LTP induction is hard and LTD easy, if low then opposite
What does the mechanism that allows a shift in the modification threshold involve?
NMDARs
What are NMDARs responsible for?
NMDARs responsible for induction of LTP and LTD come in different “flavours”, different subunit composition
NMDAR composition in highly active postsynaptic neurons favours…
LTD over LTP, and NMDAR composition in low active postsynaptic neurons favours LTP over LTD
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