GABABR silencing of nerve terminals

Abstract

Control of neurotransmission efficacy is central to theories of how the brain computes and stores information. Presynaptic G-protein coupled receptors (GPCRs) are critical in this problem as they locally influence synaptic strength and can operate on a wide range of time scales. Among the mechanisms by which GPCRs impact neurotransmission is by inhibiting voltage-gated calcium (Ca2+) influx in the active zone. Here, using quantitative analysis of both single bouton Ca2+ influx and exocytosis, we uncovered an unexpected non-linear relationship between the magnitude of action potential driven Ca2+ influx and the concentration of external Ca2+ ([Ca2+]e). We find that this unexpected relationship is leveraged by GPCR signaling when operating at the nominal physiological set point for [Ca2+]e, 1.2 mM, to achieve complete silencing of nerve terminals. These data imply that the information throughput in neural circuits can be readily modulated in an all-or none fashion at the single synapse level when operating at the physiological set point.

Astrocyte Calcium Signaling Shifts the Polarity of Presynaptic Plasticity

“…Whether the switch in polarity observed in our culture system involves the same set of synapses contributing to mEPSC depression remains to be determined, for instance by monitoring presynaptic strengths of individual synapses with fluorescent probes (e.g. Cook and Ryan, 2023) before and after NMDA + Gly application.…”