Revealing the connectivity and functionality of brain stem circuits

 描述（由申请人提供）：脑干中的神经元回路除了通过味觉、嗅觉和触觉驱动和门控主动感觉外，还控制生命维持功能。我们建议利用分子和遗传工具的出现来进行细胞谱系标记，细胞表型，分子连接组学，以及机器学习和图像处理的方法来构建脑干的综合解剖和功能图谱。这将使我们能够生成控制或面部动作的脑干回路的解剖接线图。这项工作分为三个阶段。(1)揭示的身份和组织 脑干核团脊髓和脑干的发育计划之间的惊人的相似性的动机，我们将拥抱和扩展这些努力，询问神经元的分子组成，定义在小鼠脑干中的感觉运动回路的单个核。(2)揭示脑干神经元回路及其相互作用。我们将利用跨突触病毒标记来划定由面神经、三叉神经、舌下神经和喉运动核支配的特定肌肉的通路。这将揭示迄今未知的脑干回路，包括更高脑区的调制位点。(3)控制已识别反馈电路的行为。我们将使用一组遗传工具来操纵特定的脑干神经元群体，以描绘或面部运动动作和运动协同作用。 上述努力的结果将是神经元功能组织的定量图 在脑干中，使研究计算的基础或面部行为。对这些基本行为的理解直接关系到神经系统如何处理可以自主执行但必须协同互动的计算这一更普遍的问题。因此，我们提出的脑干回路和动力学计划将产生关于神经元计算性质的一般课程。根据这一建议进行的工作将作为脑干神经元计算的更大的国家努力的基础。

 DESCRIPTION (provided by applicant): Neuronal circuits in the brainstem control life-sustaining functions, in addition to driving and gating active sensation through taste, smell, and touch. We propose to exploit the advent of molecular and genetic tools to undertake cell lineage marking, cell phenotyping, molecular connectomics, and methods from machine learning and image processing to construct an integrated anatomical and functional atlas of the brainstem. This will enable us to generate anatomical wiring diagrams for the brainstem circuits that control or facial actions. There are three phases to this work. (1) Reveal the identity and organization of brainstem nuclei. Motivated by striking similarities between the developmental plan for the spinal cord and brainstem, we will embrace and extend these efforts to interrogate the molecular composition of neurons that define individual nuclei with sensorimotor circuits in the murine brainstem. (2) Reveal brainstem neuronal circuits and their interactions. We will utilize Tran synaptic viral labeling to delimit pathways from specific muscles that are innervated by facial, trigeminal, hypoglossal, and laryngeal motor nuclei. This will reveal hitherto unknown brainstem circuits, including sites of modulation by higher brain areas. (3) Control the behavior of identified feedback circuits. We will manipulate specific populations of brainstem neurons using a battery of genetic tools to delineate or facial motor actions and motor synergies. The results from the above efforts will be a quantitative map of the functional organization of neurons in the brainstem that enable studies on computations that underlie or facial behavior. An understanding of these fundamental behaviors bears directly on the more general issue of how nervous systems deal with computations that can be performed autonomously, yet must interact synergistically. Thus our proposed program on brainstem circuitry and dynamics will yield general lessons about the nature of neuronal computation. The work performed under this proposal will serve as the basis for a larger national effort in brainstem neuronal computation.