Molecular and Functional Characterization of the Respiratory Motor Circuit

描述(申请人提供)：呼吸运动神经元(MN)的起源和形成呼吸运动回路的遗传程序仍然不清楚，尽管我们实验室和其他人最近的工作表明，它们都来自下轴运动柱(HMC)。目前还不知道呼吸MN在发育中的脊髓中是如何在分子和功能上组织的，特别是在吸气和呼气功能方面。为了开始解决这个问题，我的研究首先试图定义与HMC/呼吸MN发育相关的遗传程序，并将其细分为吸气和呼气亚组。这将通过绘制我发现的一组基因的表达图来完成，这些基因在HMC MNS中选择性表达，并评估一个基因Pou3f1的功能，该基因与吸气亚群的形成有关。同时，我将研究这些呼吸MN组被起源于脑干的下行运动前输入选择性地神经支配的逻辑。为了理解这一逻辑，我将描述当HMC MN的数量或位置改变时，这种连接的解剖学、电生理学和行为学方面的特征。通过这项研究计划，我将对呼吸MN的分子和功能组织以及这种安排是如何正确组装呼吸马达电路的关键布局提供新的见解。

DESCRIPTION (provided by applicant): The origins of respiratory motor neurons (MNs) and the genetic programs that underlie the formation of the respiratory motor circuit remain poorly defined, though recent work from our lab and others suggests that they all emerge from the hypaxial motor column (HMC). It is not yet known how the respiratory MNs are organized in the developing spinal cord molecularly and functionally, particularly in terms of inspiratory and expiratory functions. To begin addressing this question, my research seeks to define first the genetic program associated with HMC/respiratory MN development and their subdivision into inspiratory and expiratory subgroups. This will be accomplished by mapping the expression of a collection of genes that I have found are selectively expressed in HMC MNs, and evaluating the function of one gene, Pou3f1, which is associated with the formation of the inspiratory subgroup. In parallel, I will investigate the logic by which these respiratory MN groups are selectively innervated by descending premotor inputs originating in the brainstem. To understand this logic, I will characterize the anatomical, electrophysiological, and behavioral aspects of this connection when the number or position of HMC MNs has been altered. Through this research plan, I will provide novel insights into the molecular and functional organization of the respiratoy MNs and how this arrangement is the critical layout for the proper assembly of the respiratory motor circuit.