The role of patterned spontaneous network activity in motor circuit activity

神经系统使用神经回路来产生认知和行为。这些电路经常被打乱 在脊髓损伤或中风中，并且在精神障碍中是异常的。治疗这些疾病的一种方法是重新- 生长或修改神经回路因此，了解神经回路是如何组装的可能有助于设计 再生疗法和脑刺激疗法来治疗精神疾病。在电路组装期间， 神经系统表现出模式化自发网络活动（PaSNA）。PaSNA是建立一个 脊椎动物和无脊椎动物的功能电路，但我们对机制知之甚少， 涉案我的策略是利用果蝇胚胎和幼虫的运动作为一个系统来揭示 PaSNA促进神经回路组装的潜在分子和细胞机制。问世 果蝇中的新工具，如光遗传学试剂，Gal 4线操纵中央单个神经元， 神经系统（CNS）和整个CNS的透射电子显微镜连接体使其成为一个 研究神经回路的强大系统。与脊椎动物类似，运动前神经元也是PaSNA所必需的。 这就提出了这个提议所要解决的问题：哪些特定的中间神经元群体产生 不同的中间神经元有不同的活动模式吗？ 电机电路开发？通过使用我们系统特有的Gal 4系和遗传编码的钙， 指标，我将确定参与PaSNA的interneurons。我将使用所需的特征电路 与光遗传学工具一起鉴定PaSNA在建立回路中的作用 连接性和功能。该提议将揭示（1）在脑缺血时产生PaSNA的神经元成分。 运动回路组装，（2）PaSNA是否是随机的或刻板的人口活动 神经元，（3）神经元身份和参与PaSNA之间是否存在相关性;（4）是否 运动回路的建立需要PaSNA;（5）运动回路的建立是否需要PaSNA 电路功能这些代表了关键的进展，将提供深入了解的形成和功能， 果蝇和哺乳动物的神经回路，其中PaSNA是神经回路的保守元件 阵

The nervous system uses neural circuits to generate cognition and behavior. These circuits are often disrupted in spinal cord injury or stroke, and are aberrant in mental disorders. One way to treat these conditions is to re- grow or modify neural circuits. Thus, understanding how neural circuits are assembled may aid in the design of regenerative therapies, and brain stimulation therapies to treat mental disorders. During circuit assembly, nervous systems exhibit patterned spontaneous network activity (PaSNA). PaSNA is necessary to build a functional circuit in vertebrates and invertebrates, yet we know surprisingly little about the mechanisms involved. My strategy is to use Drosophila embryonic and larval locomotion as a system to uncover the underlying molecular and cellular mechanisms by which PaSNA promotes neural circuit assembly. The advent of new tools in Drosophila, such as optogenetic reagents, Gal4 lines to manipulate single neurons in the central nervous system (CNS), and a transmission electron microscopy connectome of the entire CNS make this a powerful system for studying neural circuits. Similar to vertebrates, premotor neurons are required for PaSNA. This raises the questions that this proposal addresses: Which specific interneuron populations generate PaSNA, do different interneurons have different patterns of activity, and how does interneuron PaSNA drive motor circuit development? With the use of Gal4 lines unique to our system and genetically encoded calcium indicators, I will identify the interneurons participating in PaSNA. I will use a characterized circuit required for larval locomotion together with optogenetic tools to identify the effect of PaSNA in establishing circuit connectivity and function. This proposal will reveal (1) the neuronal components that generate PaSNA during locomotor circuit assembly, (2) whether PaSNA is stochastic or stereotypic with the population of active neurons, (3) whether there is a correlation between neuronal identity and participation in PaSNA; (4) whether PaSNA is required for locomotor circuit establishment, and (5) whether PaSNA is required for locomotor circuit function. These represent critical advances that will provide insight into the formation and function of neural circuits in both Drosophila and mammals, where PaSNA is a conserved element of neural circuit formation.