Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans
Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans
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DOI：
10.1073/pnas.1621274114
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发表时间：
2017-02-14
影响因子：
11.1
通讯作者：
Bargmann, Cornelia I.
中科院分区：
文献类型：
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作者：
Jang, Heeun;Levy, Sagi;Bargmann, Cornelia I.
在秀丽隐杆线虫中，由间隙连接连接的神经元的轴辐式电路控制聚集行为和对氧、信息素和食物的相关行为反应。连接RMG中枢神经元与感觉辐条神经元的差距连接的分子组成尚不清楚。我们发现，在RMG中枢神经元中，连接蛋白基因unc-9是驱动聚集和相关行为所必需的，这表明含有UNC-9的间隙连接介导RMG信号传导。为了详细剖析这个回路，我们开发了一些方法，用显性负性的unc-1转基因来抑制基于unc-9的缝隙连接。unc-1（dn）改变了调节unc-9电信号的气孔蛋白样蛋白;其破坏性作用可以被组成型活性的GFP-9：：GFP蛋白拯救，证明了特异性。unc-1（dn）在RMG中枢神经元、ADL或ASK信息素感受神经元或URX氧感受神经元中的表达破坏了聚集相关行为的特定元素。在ADL中，unc-1（dn）具有与破伤风毒素轻链相反的作用，分离ADL电突触和化学突触的作用。这些结果揭示了缝隙连接在细胞分辨率的复杂行为中的作用，并为其他缝隙连接电路的类似探索提供了工具。
A hub-and-spoke circuit of neurons connected by gap junctions controls aggregation behavior and related behavioral responses to oxygen, pheromones, and food in Caenorhabditis elegans. The molecular composition of the gap junctions connecting RMG hub neurons with sensory spoke neurons is unknown. We show here that the innexin gene unc-9 is required in RMG hub neurons to drive aggregation and related behaviors, indicating that UNC-9containing gap junctions mediate RMG signaling. To dissect the circuit in detail, we developed methods to inhibit unc-9based gap junctions with dominant-negative unc-1 transgenes. unc-1(dn) alters a stomatin-like protein that regulates unc-9 electrical signaling; its disruptive effects can be rescued by a constitutively active UNC-9::GFP protein, demonstrating specificity. Expression of unc-1(dn) in RMG hub neurons, ADL or ASK pheromone-sensing neurons, or URX oxygen-sensing neurons disrupts specific elements of aggregation-related behaviors. In ADL, unc-1(dn) has effects opposite to those of tetanus toxin light chain, separating the roles of ADL electrical and chemical synapses. These results reveal roles of gap junctions in a complex behavior at cellular resolution and provide a tool for similar exploration of other gap junction circuits.