Molecular and Functional Characterization of the Respiratory Motor Circuit

呼吸运动回路的分子和功能表征

基本信息

批准号：
8596710
负责人：
Albert Yoon-Kyu Han
金额：
$ 3.51万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8596710
关键词：
Abdominal Muscles Address Area Axon Behavioral Biological Models Brain Stem Breathing Cells Characteristics Classification Code Collection Data Set Development Gene Expression Profile Gene Expression Profiling Generic Drugs Genes Genetic Programming Goals Intercostal Muscles Knowledge Lateral Limb structure Locomotion Logic Lung Maps Microarray Analysis Molecular Molecular Profiling Motor Motor Neurons Movement Mus Muscle Mutant Strains Mice Nervous system structure Neuraxis Neurons Peripheral Phenotype Play Population Positioning Attribute Process Property Research Respiratory Diaphragm Respiratory Muscles Respiratory physiology Role Spinal Spinal Cord Spinal Cord Column Subgroup Synapses System Ventral Horn of the Spinal Cord Work base gain of function in vivo injured insight loss of function molecular marker motor control motor neuron development mutant nerve supply neuronal cell body novel novel therapeutics public health relevance repaired research study respiratory segregation selective expression transcription factor

项目摘要

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.

描述（由申请人提供）：呼吸运动神经元（MN）的起源和呼吸运动回路形成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列（HMC）。目前尚不清楚呼吸微神经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及其细分为吸气和呼气亚组。这将通过绘制我发现在 HMC MN 中选择性表达的一组基因的表达图谱，并评估一个基因 Pou3f1 的功能来完成，该基因与吸气亚组的形成相关。同时，我将研究这些呼吸 MN 组通过源自脑干的下行前运动输入选择性神经支配的逻辑。为了理解这个逻辑，我将描述当 HMC MN 的数量或位置发生改变时这种连接的解剖学、电生理学和行为方面的特征。通过这个研究计划，我将提供关于呼吸运动神经元的分子和功能组织的新颖见解，以及这种排列如何成为呼吸运动回路正确组装的关键布局。