Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94304-5453, USA; Howard Hughes Medical Institute.
Neuron. 2017 May 17;94(4):826-839.e3. doi: 10.1016/j.neuron.2017.04.020.
Synchronous release triggered by Ca binding to synaptotagmin-1, -2, or -9 is thought to drive fast synaptic transmission, whereas asynchronous release induced by Ca binding to synaptotagmin-7 is thought to produce delayed synaptic signaling, enabling prolonged synaptic computations. However, it is unknown whether synaptotagmin-7-dependent asynchronous release performs a physiological function at fast synapses lacking a prolonged signaling mode, such as the calyx of Held synapse. Here, we show at the calyx synapse that synaptotagmin-7-dependent asynchronous release indeed does not produce a prolonged synaptic signal after a stimulus train and does not contribute to short-term plasticity, but induces a steady-state, asynchronous postsynaptic current during stimulus trains. This steady-state postsynaptic current does not increase overall synaptic transmission but instead sustains reliable generation of postsynaptic spikes that are precisely time locked to presynaptic spikes. Thus, asynchronous release surprisingly functions, at least at some synapses, to sustain high-fidelity neurotransmission driven by synchronous release during high-frequency stimulus trains.
被认为驱动快速突触传递的是 Ca 结合突触融合蛋白-1、-2 或-9 引发的同步释放，而 Ca 结合突触融合蛋白-7 引发的异步释放被认为产生延迟的突触信号，从而实现长时间的突触计算。然而，尚不清楚在缺乏长时间信号模式的快速突触（如 Held 神经球突触）中，突触融合蛋白-7 依赖性异步释放是否具有生理功能。在这里，我们在 Held 神经球突触上表明，突触融合蛋白-7 依赖性异步释放确实不会在刺激序列后产生长时间的突触信号，也不会影响短期可塑性，但会在刺激序列期间诱导稳态的异步突触后电流。这种稳态的突触后电流不会增加整体的突触传递，但会维持可靠的突触后尖峰的产生，这些尖峰与突触前尖峰精确时间锁定。因此，异步释放令人惊讶地在某些突触中发挥作用，至少在某些突触中，它在高频刺激序列期间通过同步释放来维持高保真的神经传递。
