Presynaptic function

what are vesicles?

balls of lipid membrane filled with neurotransmitter

what is the roles of the membrane bound proteins contained within the vesicles?

• for filling the vesicle with neurotransmitter
• for docking at presynaptic membrane
• for releasing the neurotransmitter

what transports neurotransmitters into vesicles ?

neurotransmitters are transported into the vesicle by a protein called proton 'antiporters'

how does neurotransmitter get into vesicles, process?

1. ATPase creates a proton gradient between the inside and outside the vesicle
2. where ATPase breaking down ATP produces energy to move the H+ into the vesicle- creating a proton electrochemical gradient
3. the proton antiporters then exchange the H+ for neurotransmitter by using the electrochemical gradient

what does an action potential first do upon arriving to the presynaptic knob? and how does it cause neurotransmitter release?

depolarises the membrane, opening voltage-gated Ca2+ channels- causing the fusion of the vesicles with the presynaptic membrane, leading to the release of them into the cleft

what classes of voltage gated calcium channels are most important for pre-synaptic Ca2+ terminal entry?

N-type & P/Q-type

what class of proteins mediate vesicle fusion with the presynaptic membrane?

SNARE proteins

what is the 3 stages of presynaptic membrane to vesicle fusion?

1. vesicles move to presynaptic active zone and dock at the plasma membrane
2. SNARE proteins on the vesicle interact with the plasma membrane and drive vesicle fusion
3. the neurotransmitter is then released into the cleft

what 2 key proteins are involved in recycling vesicles following ejection of neurotransmitter?

Dynamin and Clathrin

what does Clathrin do to the vesicle?

helps reform the vesicle

what does dynamin do to the vesicle?

closes the hole that fusing with the membrane left

where are action potentials initiated?

the axon initial segment

why can the axon initial segment initiate action potentials?

because it has a very high density of voltage-gated Na+ channels

where are synapses located?

on the axon at both: the boutons terminaux (the terminals) & the en passant boutons (along the axon)

is release probability (Pr) the same at all synapses, yes or no?

no, in fact each bouton has an unfixed & changeable Pr

what does an increased release probability (Pr) indicate?

increased synaptic strength

what does an decreased release probability (Pr) indicate?

decreased synaptic strength

what does it mean if Pr= 0?

there is no synaptic communication

what is the release probability ratio/equation?

Pr= mean no. of synapses releasing per trial/ total no. of  synapses

what can experimentally alter the release probability (Pr)?

By changing Presynaptic [Ca2+] 1) changing the extracellular Ca2+ concentration 2) applying blockers of presynaptic Ca2+ channels 3) activating presynaptic receptors that alter Ca2+ channel activity (e.g. GPCRs)

what is short-term synaptic plasticity, and what underpins it?

Short-lived changes in the strength of synaptic transmission, that are underpinned by dynamic changes in release probability (Pr)

what is a measure of short-term plasticity?

paired-pulse ratio

what type of paired pulse do synapses with low Pr exhibit?

paired pulse facilitation (second pulse larger after)

what type of paired pulse do synapses with high Pr exhibit?

paired pulse depression (second pulse smaller)

where is the readily releasable pool of vesicles in the presynaptic cleft?

docked at the active zone of the terminal, adjacent to the cleft

what determines short term plasticity?

the number of vesicles released

why is the 2nd pulse larger in paired-pulse facilitation?

1) elevated residual Ca2+ in presynaptic terminal from the 1st AP 2) vesicles available in the readily releasable pool 3) more vesicles released in the response to the 2nd AP

why is the 2nd pulse smaller in paired-pulse depression?

1) elevated residual Ca2+ in presynaptic terminal from the 1st AP 2) fewer vesicles available in the readily releasable pool 3) less vesicles released in the response to the 2nd AP