The function of gap junctions and chemical synapses in a simple neural circuit

线虫的运动神经回路是破译回路和行为基因基础的极佳模型。 以前的研究已经给出了这种电路的详细接线图，并提出了两对前置电机 中间神经元AVA和AVB通过激活A型和B型胆碱能运动在运动中起关键作用 神经元(A-MN和B-MN)。然而，各种神经元在突触水平上是如何相互作用的 很大程度上是未知的。我们最近在电压钳制运动神经元和记录缝隙连接电流方面取得的成功 蠕虫中的神经元之间的相互作用使人们有可能研究原本无法接触到的电路的特性。 我们的初步研究揭示了运动回路的几个意想不到的新奇特性，包括 运动前中间神经元和运动神经元之间的逆行缝隙连接电流 退行性变/上皮钠通道(DEG/ENaC)在B-MNS中作为牵张受体的逆行调节 反向电路的GaB能MN(D-MN)，以及左右AVA之间的电耦合 中间神经元。这一建议是使用电生理、遗传、分子和行为的组合 测试新模型的方法有三个具体目标。目标1是检验B-MNS激活的假设 AVB运动前神经元通过缝隙连接，而B-MN的活动依赖于伸展受体。我们会 确定缝隙结整流的分子机制和弱电耦合的影响 对AVB活动和运动行为的影响。我们将确定B-MNS中可能的DEG/ENaC并确定其 在B-MN活动和运动中的作用。目的二是研究分子间的整流耦合机制。 AVA和A-MNS，以及左右AVA中间神经元之间电耦合的生理作用。 我们将确定整改是否由AVA中UNC-7内联蛋白的N端授予，以及是否 破坏AVA中间神经元之间的耦合会改变运动行为。目标3是检验假设 D-MNS通过AVA逆行抑制A-MNS，AVB通过抑制AVA促进前向运动。 我们将评估干扰新的D-MN抑制电路对运动的影响。我们将确定 突触后受体介导AVB对AVA的抑制作用，并分析破坏该受体的作用 在移动中。这个项目可能会重塑我们对线虫运动神经回路的理解，并且 帮助我们接近阐明行为的回路和基因基础的长期目标。

C. elegans locomotion neural circuit is an excellent model for decoding the circuit and gene bases of behaviors. Previous studies have produced a detailed wiring diagram of this circuit, and proposed that two pairs of premotor interneurons, AVA and AVB, play key roles in locomotion by activating A-type and B-type cholinergic motor neurons (A-MNs and B-MNs), respectively. However, how the various neurons interact at the synaptic level is largely unknown. Our recent success in voltage-clamping motor neurons and recording gap junction currents between neurons in worms makes it possible to look into properties of the circuit that are otherwise inaccessible. Our preliminary studies revealed several unexpected and novel properties of the locomotion circuit, including retrograde gap junction currents between the premotor interneurons and motor neurons, a putative degenerin/epithelial sodium channel (DEG/ENaC) serving as a stretch receptor in B-MNs, retrograde regulation of the backward circuit by GABAergic MNs (D-MNs), and electrical coupling between the left and right AVA interneurons. This proposal is to use a combination of electrophysiological, genetic, molecular, and behavioral approaches to test a new model with three specific aims. Aim 1 is to test the hypotheses that B-MNs activate AVB premotor interneurons through gap junctions, and that B-MN activity depends on a stretch receptor. We will determine molecular mechanisms of the gap junction rectification and the effects of deficient electrical coupling on AVB activity and locomotion behavior. We will identify the putative DEG/ENaC in B-MNs and determine its roles in B-MN activity and locomotion. Aim 2 is to investigate the mechanism of the rectifying coupling between AVA and A-MNs, and the physiological role of electrical coupling between the left and right AVA interneurons. We will determine whether the rectification is conferred by the N-terminal of UNC-7 innexin in AVA and whether disrupting the coupling between AVA interneurons alters locomotion behavior. Aim 3 is to test the hypotheses that D-MNs inhibit A-MNs retrogradely via AVA, and that AVB facilitates forward locomotion by inhibiting AVA. We will assess the effect of disrupting the novel D-MN inhibitory circuit on locomotion. We will identify the postsynaptic receptors mediating AVB inhibition on AVA, and analyze the effect that disrupting this receptor has on locomotion. This project may reshape our understanding of the C. elegans locomotion neural circuit, and help us approach the long-term goal of elucidating the circuit and gene bases of behaviors.