Development, Stem Cell, and Regenerative Medicine Graduate Program, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033.
Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA 90033.
Proc Natl Acad Sci U S A. 2021 May 18;118(20). doi: 10.1073/pnas.2022599118.
Electrical synapses are specialized structures that mediate the flow of electrical currents between neurons and have well known roles in synchronizing the activities of neuronal populations, both by mediating the current transfer from more active to less active neurons and by shunting currents from active neurons to their less active neighbors. However, how these positive and negative functions of electrical synapses are coordinated to shape rhythmic synaptic outputs and behavior is not well understood. Here, using a combination of genetics, behavioral analysis, and live calcium imaging in , we show that electrical synapses formed by the gap junction protein INX-1/innexin couple the presynaptic terminals of a pair of motor neurons (AVL and DVB) to synchronize their activation in response to a pacemaker signal. Live calcium imaging reveals that /innexin mutations lead to asynchronous activation of AVL and DVB, due, in part, to loss of AVL-mediated activation of DVB by the pacemaker. In addition, loss of leads to the ectopic activation of DVB at inappropriate times during the cycle through the activation of the L-type voltage-gated calcium channel EGL-19. We propose that electrical synapses between AVL and DVB presynaptic terminals function to ensure the precise and robust execution of a specific step in a rhythmic behavior by both synchronizing the activities of presynaptic terminals in response to pacemaker signaling and by inhibiting their activation in between cycles when pacemaker signaling is low.
电突触是一种特殊的结构，介导神经元之间的电流流动，在协调神经元群体的活动方面具有重要作用，既可以通过介导从活动神经元到不活动神经元的电流传递，也可以通过将电流从活动神经元分流到其不活动的相邻神经元。然而，电突触的这些正、负功能是如何协调的，以形成有节奏的突触输出和行为，目前还不是很清楚。在这里，我们使用遗传学、行为分析和活体钙成像技术的组合，表明由间隙连接蛋白 INX-1/innexin 形成的电突触将一对运动神经元（AVL 和 DVB）的突触前末梢耦合在一起，以响应起搏信号同步它们的激活。活体钙成像揭示，/innexin 突变导致 AVL 和 DVB 的激活不同步，部分原因是起搏丧失了 AVL 对 DVB 的激活。此外，缺失 会导致 L 型电压门控钙通道 EGL-19 的激活，从而导致 DVB 在周期中的不合适时间异位激活。我们提出，AVL 和 DVB 突触前末梢之间的电突触通过响应起搏信号同步突触前末梢的活动，并在起搏信号低时抑制它们在周期之间的激活，从而确保在节律性行为的特定步骤中进行精确而稳健的执行。
