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.

项目摘要 呼吸性化学感受是大脑对响应变化而调节呼吸的机制 在CO2/H+中。这种机制对于无意识地维持呼吸至关重要，其破坏是 与呼吸问题有关，尤其是在睡眠期间。下丘脑长期以来一直是 被认为是化学感受器区域；但是，该功能的基础机制知之甚少。作为 LHA神经元显示出可观的遗传变异性，可能与功能相关，我的中心假设是 LHA神经元的离散子集专门用作呼吸学化学感受器。为了测试这个，我 将使用一种新颖的遗传方法来标记和识别CO2/H+活化的LHA神经元（AIM 1）；识别固有的 和有助于LHA CO2/H+灵敏度的突触机制（AIM 2），并确定这些贡献 细胞至基线呼吸和对CO2的通气反应（AIM 3）。这项工作的重要结果 包括1）确定LHA如何贡献CO2/H+依赖性的细胞和网络基础 呼吸，2）告知LHA功能异质性，3）提供有价值的分子，细胞和 整个动物的方法应该使我能够迈出下一步朝着我的目标迈出目标 成为独立研究者。