Identification of chemosensitive cells within the lateral hypothalamus

项目摘要 呼吸化学感受是大脑调节呼吸以响应变化的机制 二氧化碳/氢离子。这种机制对于无意识地维持呼吸至关重要， 与呼吸问题有关，特别是在睡眠期间。外侧下丘脑长期以来 被认为是化学感受器区域;然而，对该功能的机制知之甚少。作为 LHA神经元显示出相当大的遗传变异性，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作为呼吸化学感受器发挥作用。为了验证这个，我 将使用一种新的遗传方法来标记和鉴定CO2/H+激活的LHA神经元（目的1）; 和突触机制有助于LHA CO2/H+敏感性（目的2），并确定这些贡献 细胞对基线呼吸和对CO2的呼吸反应（目标3）。这项工作的重要成果 包括1）确定LHA如何有助于CO2/H+依赖的细胞和网络基础， 呼吸，2）告知LHA功能异质性，以及3）提供分子，细胞和 整个动物的方法，应该使我很好地定位采取下一步对我的目标， 成为独立调查员。

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.