Regulation of synaptic release‐site Ca²⁺ channel coupling as a mechanism to control release probability and short‐term plasticity

Abstract

Synaptic transmission relies on the rapid fusion of neurotransmitter-containing synaptic vesicles (SVs), which happens in response to action potential (AP)-induced Ca influx at active zones (AZs). A highly conserved molecular machinery cooperates at SV-release sites to mediate SV plasma membrane attachment and maturation, Ca sensing, and membrane fusion. Despite this high degree of conservation, synapses - even within the same organism, organ or neuron - are highly diverse regarding the probability of APs to trigger SV fusion. Additionally, repetitive activation can lead to either strengthening or weakening of transmission. In this review, we discuss mechanisms controlling release probability and this short-term plasticity. We argue that an important layer of control is exerted by evolutionarily conserved AZ scaffolding proteins, which determine the coupling distance between SV fusion sites and voltage-gated Ca channels (VGCC) and, thereby, shape synapse-specific input/output behaviors. We propose that AZ-scaffold modifications may occur to adapt the coupling distance during synapse maturation and plastic regulation of synapse strength.

Bridging Biological and Artificial Neural Networks with Emerging Neuromorphic Devices: Fundamentals, Progress, and Challenges

“…[60][61][62] Finally, chloride (Cl − ) channels regulate the membrane excitability, repolarize APs, stabilize the resting voltage, and regulate the IPSC. Ca 2+ entry to a presynaptic terminal is mainly through voltage-gated Ca 2+ channels (CaV) and can trigger neurotransmitter release from the active zone.…”

“…Ca 2+ entry to a presynaptic terminal is mainly through voltage-gated Ca 2+ channels (CaV) and can trigger neurotransmitter release from the active zone. [60][61][62] Finally, chloride (Cl − ) channels regulate the membrane excitability, repolarize APs, stabilize the resting voltage, and regulate the IPSC. [57]…”

A sensory cell diversifies its output by varying Ca2+ influx-release coupling among presynaptic active zones for wide range intensity coding

“…Lastly, differences in Ca 2+ channel-exocytosis coupling could affect the short-term plasticity (ref. 56 ), note the higher adaptation strength of high-SR SGNs in vivo (ref. 57 ).…”

Post-tetanic potentiation lowers the energy barrier for synaptic vesicle fusion independently of Synaptotagmin-1

“…Several mechanisms have been proposed for synaptic plasticity, including ways to increase the presynaptic Ca 2+ signal (for review see [27]), (activity dependent) channel-attachment of vesicles [86,87], Ca 2+ dependent vesicle priming [42,43] or inhibition of un-priming [69], and tightening of the SNARE-complex [78]. Our model employs a single mechanistic principle, multiplicative modulation of fusion rates through additive modulation of the energy barrier, to describe supralinear Ca 2+ -sensitivity of release and PTP.…”