Revealing the connectivity and functionality of brain stem circuits

点击翻译按钮获取中文摘要

 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.