Identification of chemosensitive cells within the lateral hypothalamus

下丘脑外侧化学敏感细胞的鉴定

• 批准号: 10672165
• 负责人: MAGGIE ANN KHUU
• 金额: $ 4.27万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10672165
• 关键词: Anatomy; Animals; Arousal; Behavior; Brain; Brain Stem; Brain region; Breathing; Carbon Dioxide; Cell Nucleus; Cells; Chemoreceptors; Data; Electrophysiology (science); Foundations; Genetic; Goals; Heterogeneity; Homeostasis; Hypothalamic structure; In Vitro; Infusion procedures; Label; Lateral; Mediating; Metabolic; Metabolism; Microdialysis; Modality; Molecular; Mus; Neurons; Outcome; Positioning Attribute; Rabies; Regulation; Research; Research Personnel; Respiratory Center; Respiratory physiology; Role; Sensory; Sleep; Sleep Apnea Syndromes; Slice; Source; Synapses; Techniques; Testing; Training; Unconscious State; Work; awake; cell type; energy balance; genetic approach; hypocretin; in vivo; novel; respiratory; response; transcriptomics; uptake; wasting

PROJECT SUMMARY Respiratory chemoreception is the mechanism by which the brain regulates breathing in response to changes in CO2/H+. This mechanism is essential for maintaining breathing unconsciously and its disruption is associated with breathing problems particularly during sleep. The lateral hypothalamus has long been considered a chemoreceptor region; however, mechanisms underlying this function are poorly understood. As LHA neurons show considerable genetic variability that may correlate with function, my central hypothesis is that discrete subsets of LHA neurons are specialized to function as respiratory chemoreceptors. To test this, I will use a novel genetic approach to label and identify CO2/H+ activated LHA neurons (Aim 1); identify intrinsic and synaptic mechanisms contributing to LHA CO2/H+ sensitivity (Aim 2), and determine contributions of these cells to baseline breathing and the ventilatory response to CO2 (Aim 3). Important outcomes of this work include 1) determining the cellular and network basis for how the LHA contributes to the CO2/H+ dependent breath, 2) inform about LHA functional heterogeneity, and 3) provide valuable training in molecular, cellular and whole animal approaches that should make me well positioned for taking the next step towards my goal of becoming an independent investigator.

项目总结 呼吸化学接收是大脑调节呼吸以应对变化的机制。 单位：CO2/H+。这种机制对于保持无意识的呼吸是必不可少的，它的破坏是 与呼吸问题有关，尤其是在睡眠期间。长期以来，外侧下丘脑 被认为是化学感受器区域；然而，这一功能的潜在机制却知之甚少。AS LHA神经元表现出相当大的遗传变异性，这可能与功能相关，我的中心假设是 LHA神经元的离散亚群专门作为呼吸化学感受器发挥作用。为了测试这一点，我 将使用一种新的遗传方法来标记和识别CO2/H+激活的LHA神经元(目标1)；识别固有的 以及促进LHA CO2/H+敏感性的突触机制(目标2)，并确定这些机制的贡献 细胞对基线呼吸和对二氧化碳的呼吸反应(目标3)。这项工作的重要成果 包括1)确定LHA如何促进CO2/H+依赖的蜂窝和网络基础 呼吸，2)告知LHA功能异质性，以及3)提供有价值的分子、细胞和 全力以赴的方法，应该会让我处于有利地位，朝着我的目标迈出下一步 成为一名独立调查员。