Control of trigeminal touch sensory circuit assembly

描述（由申请人提供）：啮齿动物使用胡须作为主要的触觉传感器。单个须由位于三叉神经节的一组触觉感觉神经元支配，并由来自同一组三叉神经元的中央轴突映射到大脑。20世纪70年代发现的与须相关的大型模块化结构（后脑中的桶状体，丘脑中的桶状体和皮层中的桶状体）使三叉须系统成为研究体感图和触觉感觉回路的流行原型模型。然而，到目前为止，我们对每个晶须代表单元内组装的精确神经回路的了解仍然有限。本提案的目的是剖析由不同类别的触觉感觉神经元在单个小管内形成的微电路，并开始确定控制这些小管电路精确组装的分子机制。这些研究将为未来理解体感信息编码和处理以及最终的感觉知觉提供急需的知识。这项研究揭示的机制也将对理解与体感觉系统异常连接相关的神经病理疾病（如自闭症和神经性口面部疼痛）具有广泛的意义。与视觉和嗅觉感觉系统的进展相比，我们对各种体感神经元之间的精确突触连接以及控制体感回路组装的机制知之甚少。在这项拨款申请中，我们将以小鼠三叉神经系统为模型，解剖代表触觉器官的详细神经回路-胡须，并开始识别控制小鼠大脑内触觉感觉回路形成的分子机制。本研究揭示的神经回路和机制不仅揭示了体感系统组织和发展的一般原理，而且对理解与体感系统异常连接相关的神经病理疾病，如自闭症疾病和神经性口面部疼痛，具有广泛的意义。

DESCRIPTION (provided by applicant): Rodents use whiskers as their primary tactile sensors. Individual whiskers are innervated by a group of touch sensory neurons located in the trigeminal ganglion, and are mapped onto the brain by the central axons from the same set of trigeminal neurons. The discovery of the whisker- related large modular structures (barrelettes in the hindbrain, barreloids in the thalamus and barrels in the cortex) in 1970s made the trigeminal-whisker system a popular prototypic model for studying somatosensory maps and touch sensory circuits. Yet to date, we still have limited knowledge of the precise neural circuits assembled inside each whisker-representing unit. The objective of this proposal is to dissect the micro-circuits formed by different classes of touch sensory neurons within individual barrelettes, and to begin to identify the molecular mechanisms controlling the precise assembly of these barrelette circuits. These studies will provide the much- needed knowledge for future understanding of somatosensory information coding and processing and ultimately sensory perception. The mechanisms uncovered in this study will also have broad implications for understanding neuropathological diseases associated with abnormal wiring in the somatosensory system such as Autism and neuropathic orofacial pain. PUBLIC HEALTH RELEVANCE Compared with advance in the visual and olfactory sensory system, we know relatively little about the precise synaptic connections made by diverse somatosensory neurons and the mechanisms controlling the assembly of somatosensory circuits. In this grant proposal, we will use the mouse trigeminal system as a model to dissect the detailed neural circuits representing the tactile organs - the whiskers, and to begin to identify the molecular mechanisms controlling the formation of touch sensory circuits inside the mouse brain. The circuits and mechanisms uncovered in this study will not only reveal general principles underlying the organization and the development of the somatosensory system, but also will have broad implications for understanding neuropathological diseases associated with abnormal wiring in the somatosensory system such as Autism diseases and the neuropathic orofacial pain.