PERIAQUEDUCTAL GRAY AND CONTROL OF BREATHING DURING SLEEP

中脑导水管周围灰质外侧细胞柱 构成下丘脑区域之间的主要解剖学联系， 在延髓内的睡眠-觉醒控制和呼吸控制部位。 刺激PAG可以改变呼吸和具有呼吸- 在灵长类动物的PAG中已经确定了相关的放电， 猫 我们假设下丘脑的睡眠-觉醒控制机制调节 延髓呼吸控制系统，部分通过对PAG的影响 神经元具体来说，我们假设γ-氨基丁酸（GABA）- 含有来自视前下丘脑前区（POA）的神经元 在非快速眼动期对与癫痫相关的PAG神经元发挥抑制作用 睡吧我们以前已经证明，温度敏感神经元是一种 POA睡眠控制机制的关键组成部分，我们假设 局灶性POA变暖将增强GABA介导的PAG抑制， 与谋杀有关的活动。 为了验证这些假设，我们将：1）记录直接 大鼠和猫中从POA到PAG的GABA能投射; 2） 确定PAG微量输注抑制呼吸的能力， 大鼠和猫在清醒和睡眠期间的上气道肌肉活动; 3） 记录与神经元活动相关的状态依赖性 在侧PAG细胞列内使用慢性微线记录 技术，并确定是否在快速眼动睡眠中观察到的变化 类似于轻度下丘脑警告引起的; 4）试图 预防非REM睡眠相关和POA变暖诱导的PAG变化 通过同时递送GABA受体拮抗剂， 通过相邻的微透析探针记录PAG微丝位点。 拟议的研究将是第一个直接审查参与的 状态依赖性呼吸中广泛的POA>PAG>延髓通路 控制它们将有助于描述功能性神经解剖学的特征， 睡眠中正常和紊乱呼吸的神经药理学。

The lateral cell columns of the midbrain periaqueductal gray (PAG) constitute a major anatomical link between hypothalamic regions implicated in sleep-wake control and respiratory control sites within the medulla. Stimulation of the PAG can alter respiration and neurons with respiratory- related discharge have been identified within the PAG of primates and cats. We hypothesize that hypothalamic sleep-wake control mechanisms modulate medullary respiratory control systems, in part, via effects on PAG neurons. Specifically, we hypothesize that gamma-aminobutyric acid (GABA)- containing neurons from the preoptic anterior hypothalamic area (POA) exert inhibitory effects on respiratory-related PAG neurons during non-REM sleep. We have previously demonstrated that thermosensitive neurons are a critical component of the POA sleep control mechanism, and we hypothesize that focal POA warming will enhance GABA-mediated inhibition of PAG respiratory-related activity. To test these hypotheses, we will: 1) document the extent of the direct GABAergic projection from the POA to the PAG in rats and cats; 2) determine the ability of PAG micro-infusions to suppress breathing and upper airway muscle activity in rat and cats during waking and sleep; 3) document the state dependency of respiratory-related neuronal activity within the lateral PAG cell columns using chronic micro-wire recording techniques, and determine whether or not changes observed in on-REM sleep are similar to those evoked by mild hypothalamic warning; 4) attempt to prevent non-REM sleep-related and POA-warming induced changes in PAG neuronal activity by concurrently delivering GABA-receptor antagonists to PAG micro-wire recording sites via an adjacent microdialysis probe. Proposed studies will be the first to directly examine the involvement of extensive POA>PAG> medullary pathways in state-dependent respiratory control. They will help to characterize the functional neuroanatomy and the neuropharmacology of normal and disordered breathing during sleep.