GPCR mediated regulation of synaptic transmission

Synaptic transmission is a finely regulated mechanism of neuronal communication. The release of neurotransmitter at the synapse is not only the reflection of membrane depolarization events, but rather, is the summation of interactions between ion channels, G protein coupled receptors, second messengers, and the exocytotic machinery itself which exposes the components within a synaptic vesicle to the synaptic cleft. The focus of this review is to explore the role of G protein signaling as it relates to neurotransmission, as well as to discuss the recently determined inhibitory mechanism of Gβγ dimers acting directly on the exocytotic machinery proteins to inhibit neurotransmitter release.

► This review focuses on the presynaptic regulation of neurotransmission. ► Heterotrimeric G protein signaling is an important part of that regulation. ► Gβγ has a novel means of regulating synaptic neurotransmission. ► This regulation may have a large impact on disease pathology and treatment. ► There are many open questions relating to G protein signaling and neurotransmission.