Department of Anesthesiology, Weill Cornell Medical College, New York, United States.
Department of Biochemistry, Weill Cornell Medical College, New York, United States.
Elife. 2023 Apr 4;12:e83530. doi: 10.7554/eLife.83530.
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) influx in the active zone. Here, using quantitative analysis of both single bouton Ca influx and exocytosis, we uncovered an unexpected non-linear relationship between the magnitude of action potential driven Ca influx and the concentration of external Ca ([Ca]). We find that this unexpected relationship is leveraged by GPCR signaling when operating at the nominal physiological set point for [Ca], 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.
神经递质传递效能的控制是大脑计算和存储信息理论的核心。 突触前 G 蛋白偶联受体（GPCR）在这个问题中至关重要，因为它们局部影响突触强度，并且可以在广泛的时间尺度上发挥作用。 GPCR 影响神经递质传递的机制之一是抑制活性区中的电压门控钙（Ca）内流。 在这里，我们使用单个囊泡 Ca 内流和胞吐作用的定量分析，揭示了动作电位驱动的 Ca 内流幅度与外部 Ca([Ca])浓度之间的意外非线性关系。 我们发现，当 GPCR 信号在 1.2mM 的名义生理设定点（Ca）下运行时，这种意外关系被利用来实现神经末梢的完全沉默。 这些数据表明，当在生理设定点运行时，在单个突触水平上，可以以全有或全无的方式轻松调节神经回路中的信息吞吐量。
