Synaptic Reliability and Short-Term Plasticity

reliability of ach release at NMJ

• EPP from a single motor neuron input has a peak amplitude between 40-80mV from resting

• number of active zones in a single end plate ~ 1000

• each vesicle generates a mini EPP ~ 0.4mV

• for an EPP of 40 to 80mV

  • number of vesciles per EPP is 100-200

  • 40 to 80 / 0.4 = 100-200

reliability definition for release

pr = mean number of vesicles involved in release / number of active sites

probability of release at NMJ and vesicle fusion failure

• 10-20% release

• 80-90% failure

reliability of cns

• number of primed vesicles is 2-10

• miniature EPSPs - 0.1mV

• for individual synapse its 0.01mV

• vesicle content smaller than NMJ

• 200 active zones

• glutamatergic

• produce EPSP ~-40mV

where is there a 1:1 relationship in the CNS

purkinje cell target from climbing fibres from inferior olivary nucleus

factors which affect Pr

• shape of action potential

• conversion of calcium signal to exocytosis

how does shape of AP affect Pr

1. longer, broader the AP, greater calcium influx, more likely to occur

2. open probability and rate of inactivation of calcium channels - direct modulation by GPCR

3. upregulation is Gq, downregulation is Gi

how does conversion of calcium signal to exocytosis affect Pr

1. depends on number of primed vesicles at active zone and

2. calcium responsiveness of these vesicles - calcium sensitivity to release machinery

How is synaptic plasticity measured?

• change in amplitude of a postsynaptic response (synaptic

output), synaptic strength or weight to the same level of presynaptic

activation (same stimulus input i.e., presynaptic action potential)

What is the change seen in short term synaptic plasticity?

an increase in synaptic weight i.e., EPSP / IPSP bigger

or decrease in synpatic weight so EPSP / IPSP smaller

mechanism of short term plasticity paired pulse facilitation

• 1st pulse has presynaptic action potential. opening of calcium channels

• release of calcium from vesicles

• neurotransmitter binds to create 1st postsynaptic response

• second pulse arrives later, residual calcium so total intracellular calcium is higher, second response is larger, temporary increased strength

• increased Pr (presynaptic release probability)

2 mechanisms for paired pulse facilitation

• residual calcium buildup

• ionotropic auto receptor activation

paired pulse depression

• second response is smaller than the first

• first pulse may deplete the number of vesicles so less vesicles are available for second release

• synapses strength has temp decreased

how does synapses history affect strength of transmission

• paired pulse facilitation

• paired pulse depression

paired pulse depression mechanisms

• vesicle depletion PRESYNAPTIC

• metabotropic autoreceptor activation PRESYNAPTIC

• ionotropic receptor desensitisation POSTSYNAPTIC

how does metabotropic autoreceptor activation lead to depression

• GPCR increase inactivation of Ca2+ channels

• via beta gamma dimer of G protein

• dec Pr

how does ionotropic receptor desensitisation cause depression

• after 1st AP there is inactive state - rapid EPSC decay

• typically occurs after pr is already high

examples of ionotropic receptors which desensitise

• GABA-A and AMPA

how does ionotropic autoreceptor activation cause facilitation and example receptors

• elevate background Ca2+ levels

• increases overall Ca2+ levels

• seen in nACh and NMDA-R

where is short term plasticity seen

• cerebellum - climbing fibres

• hippocampus - CA1 response to schaffer collateral activation