GABA(B)R 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 (Ca(2+)) influx in the active zone. Here, using quantitative analysis of both single bouton Ca(2+) influx and exocytosis, we uncovered an unexpected non-linear relationship between the magnitude of action potential driven Ca(2+) influx and the concentration of external Ca(2+) ([Ca(2+)](e)). We find that this unexpected relationship is leveraged by GPCR signaling when operating at the nominal physiological set point for [Ca(2+)](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.