Functional dissection of medullary respiratory microcircuits

描绘复杂行为背后的神经元是一项基本的兴趣。我们将开发一种新的方法 对于基因靶向神经元兴奋性的极快速变化，以影响强大和重要的正在进行的 啮齿动物的调节行为，即呼吸。呼吸是一种调节气体交换的非凡行为。 支持新陈代谢，调节pH值。一个可靠而有力的节奏对于哺乳动物的呼吸是必不可少的。 患有睡眠呼吸暂停、早产儿呼吸暂停的人类无法保持正常的呼吸节奏， 先天性中枢性低通气综合征、过度换气综合征、Rett综合征，可能还会突然出现 婴儿死亡综合征，会导致严重的不良健康后果，甚至死亡。各种神经退行性变 帕金森氏症、多系统萎缩和肌萎缩侧索硬化症等疾病 与睡眠呼吸障碍有关，我们推测是由于脑区神经元的丧失所致 控制呼吸。如果要在正常和病理条件下理解呼吸， 必须揭示呼吸节律发生的机制。我们将重点放在两个大脑区域 正常呼吸模式、Preb？tzinger复合体和后梯形呼吸模式的产生 核团/面旁呼吸组。利用病毒传递系统，我们将表达基因编码的视蛋白 在这些关键区域的神经元的不同表型中。这些神经元兴奋性的快速变化 在麻醉、清醒或麻醉状态下，通过植入这些部位的光纤传递的光脉冲的管理 睡眠中的老鼠应该会在呼吸中产生明显的、甚至是深刻的干扰。对这种扰动的分析 将为理解呼吸节律和模式的机制提供一个非凡的窗口 一代。

Delineating neurons that underlie complex behaviors is of fundamental interest. We will exploit a novel method for extremely rapid changes in excitability of genetically targeted neurons to affect a robust and vital ongoing regulatory behavior in rodents, i.e., breathing. Breathing is a remarkable behavior that mediates gas exchange to support metabolism and regulate pH. A reliable and robust rhythm is essential for breathing in mammals. Failure to maintain a normal breathing rhythm in humans suffering from sleep apnea, apnea of prematurity, congenital central hypoventilation syndrome, hyperventilation syndrome, Rett syndrome, and perhaps sudden infant death syndrome, leads to serious adverse health consequences, even death. Various neurodegenerative diseases, such as Parkinson's disease, multiple systems atrophy and amyotrophic lateral sclerosis, are associated with sleep disordered breathing that we hypothesize results from the loss of neurons in brain areas controlling respiration. If breathing is to be understood in normal and in pathological conditions, the mechanisms for respiratory rhythmogenesis must be revealed. We focus on two brain sites essential for generation of the normal breathing pattern, the preB¿tzinger Complex and the retrotrapezoid nucleus/parafacial respiratory group. Using a viral delivery system, we will express genetically encoded opsins in various phenotypes of neurons in these key regions. Rapid changes in excitability of these neurons by administration of light pulses delivered via an optical fiber implanted in these sites in anesthetized, awake or sleeping rats should produce noticeable, even profound perturbations in breathing. Analysis of such perturbations will provide an extraordinary window into understanding mechanisms of respiratory rhythm and pattern generation.