GABA_BR silencing of nerve terminals

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.