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（MNS）的起源以及呼吸运动回路形成的基础的遗传程序仍然很差，尽管我们实验室的最新工作和其他工作表明它们都从Hypaxial Motor柱（HMC）中出现。尚不清楚如何在发育中的脊髓分子和功能上组织呼吸道MN，尤其是在灵感和呼气功能方面。为了开始解决这个问题，我的研究试图首先定义与HMC/呼吸道MN开发相关的遗传程序及其分为灵感和呼气亚组的细分。这将通过映射我发现的基因集合的表达来实现，并在HMC MNS中选择性地表达，并评估一个基因POU3F1的功能，该基因与灵感亚组的形成有关。同时，我将研究这些呼吸MN组通过源于脑干的降序前输入选择性支配的逻辑。为了理解这种逻辑，我将表征当HMC MN的数量或位置改变时，该联系的解剖学，电生理和行为方面。通过该研究计划，我将提供有关Respiratoy MN的分子和功能组织的新见解，以及这种布置如何成为适当组装呼吸运动电路的关键布局。