Neural circuits and synaptic mechanisms underlying behavior in C. elegans

描述（由申请人提供）：神经回路由一组神经元通过特定的突触连接组装而成，是神经系统的功能和结构单元。异常的神经回路和突触功能导致许多类型的神经系统疾病。我们感兴趣的是绘制神经回路的功能组件，解剖回路处理信息的突触机制，并了解基因如何调节这一过程以及最终如何产生和重塑行为输出。鉴于人类神经系统的巨大复杂性和遗传操作的不可及性，具有相对简单的神经系统的遗传模式生物，如C。elegans和Drosophila的基因组已经被广泛用于研究这些问题。C.由于其简单、特征明确的神经系统和易于遗传操作的特性，秀丽隐杆线虫近年来已成为研究神经生物学中各种现象的越来越受欢迎的遗传模型。值得注意的是，C.线虫是唯一已知其连接体（整个神经系统的接线图）的生物。此外，许多控制神经信号传导、加工和发育的基本原理在C.优雅大约三分之二的人类疾病基因在这种生物体中有同源物。然而，C.线虫的神经系统在功能上是有组织的，以产生行为。我们最近开发了一种自动钙成像系统，可以记录自由行为动物的神经活动。我们还开发了一种多学科方法，通过整合功能成像，光遗传学询问，遗传操作，激光消融， 和电生理学。使用这种方法，我们将映射的功能组件的运动电路，研究的突触机制，电路处理信息，并表征感觉线索如何调节电路动态调制行为输出。由于蠕虫处理信息所采用的微电路和突触机制与哺乳动物具有惊人的相似性，我们的研究将为高等生物行为的神经基础提供新的见解。

DESCRIPTION (provided by applicant): Neural circuits are assembled from a group of neurons via specific synaptic connections, and are the functional and structural units of the nervous system. Abnormal neural circuit and synaptic function lead to many types of neurological disorders. We are interested in mapping the functional components of neural circuits, dissecting the synaptic mechanisms by which the circuits process information, and understanding how genes regulate this process and how this ultimately produces and reshapes behavioral output. Given the immense complexity of the human nervous system and its inaccessibility to genetic manipulation, genetic model organisms with a relatively simple nervous system, such as C. elegans and Drosophila, have been widely used to investigate these questions. C. elegans has recently emerged as an increasingly popular genetic model for studying various phenomena in neurobiology, due to its simple and well characterized nervous system and amenability to genetic manipulation. Notably, C. elegans represents the only organism whose connectome (wiring diagram of its entire nervous system) is known. Additionally, many basic principles governing neural signaling, processing and development are conserved in C. elegans. About two-third of human disease genes have homologs in this organism. However, it remains largely enigmatic how the C. elegans nervous system is functionally organized to generate behaviors. We have recently developed an automated calcium imaging system that allows recording of neural activity in freely-behaving animals. We have also developed a multidisciplinary approach to map the neural circuits underlying behavior by integrating functional imaging, optogenetic interrogation, genetic manipulation, laser ablation, and electrophysiology. Using this approach, we will map the functional components of motor circuits, investigate the synaptic mechanisms by which the circuits process information, and characterize how sensory cues regulate the circuit dynamics to modulate behavioral output. As the microcircuits and the synaptic mechanisms employed by worms to process information show striking similarities to those by mammals, our study will provide novel insights into the neural basis of behavior in higher organisms.