CSF AND THE CENTRAL CHEMICAL CONTROL OF BREATHING

适当的呼吸需要1)中枢化学感受器对二氧化碳水平的反馈，以及2)强直的“驱动”，部分来自二氧化碳，部分来自其他来源，包括吻侧腹侧髓质（RVLM）。最近的研究表明：1)中枢化学接收存在于脑干的许多部位，2)后梯形核（RTN）是RVLM的关键部位，它提供化学接收和呼吸的强直驱动。我们问：为什么有这么多的中枢化学受体位点？它们是如何工作的？RTN在控制呼吸中的生理作用是什么？我们将在慢性非麻醉大鼠模型中使用微透析探针向RTN（或其他部位）输送物质，评估睡眠和清醒时化学受体和RTN的功能。探针尖端长1毫米，直径240毫米，体积45毫升。它允许在同一动物的同一部位重复应用神经活性物质，并连续测量通气和耗氧量（全身体积描记仪）、唤醒状态（脑电图、颈肌电图）、体温和血压（遥测），在某些情况下，还可以测量血气和ph值。大约2/3的实验使用该模型；1/3只麻醉通气大鼠，以膈活度为呼吸输出量。对于化学接受生理学的研究，我们在两种模型中通过CO2微透析产生局灶性组织酸中毒。为了研究其机制，我们在麻醉大鼠的酸中毒病灶区域内通过注射/透析改变神经功能。对于RTN的研究，我们在慢性模型中用muscimol（一种GABA-A受体激动剂）透析可逆地抑制神经元。中枢化学感受器生理是重要的；二氧化碳是呼吸控制系统的关键组成部分，疾病中的二氧化碳滞留会导致发病。化学感受和RTN功能随觉醒状态而变化，因此可能在睡眠呼吸障碍中很重要，RTN被假设为弓形核的动物同源物，在SIDS患者中被描述为异常。

Appropriate breathing requires 1) feedback concerning the level of CO2 from central chemoreceptors, and 2) a tonic 'drive', partly from CO2, and partly from other sources including the rostral ventrolateral medulla (RVLM). Recent work established that 1) central chemoreception is present at many brainstem locations, and 2) the retrotrapezoid nucleus (RTN) is a key RVLM site that provides both chemoreception and a tonic drive to breathe. We ask: Why are there so many central chemoreceptor sites? How do they work? What is the physiological role of the RTN in the control of breathing? We will evaluate chemoreceptor and RTN function during sleep and wakefulness in a chronic unanesthetized rat model using a microdialysis probe to deliver substances to the RTN (or other site). The probe tip is 1 mm in length and 240 mum in diameter, a volume of 45 nl. It allows repeated application of neuroactive substances at the same site in the same animal with continuous measurement of ventilation and oxygen consumption (whole body plethysmograph), arousal state (EEG, nuchal EMG), body temperature and blood pressure (telemetry), and, in some cases, blood gases and pH. Approximately 2/3 of the experiments use this model; 1/3 an anesthetized, ventilated rat with phrenic activity as the measure of respiratory output. For studies of chemoreception physiology, we produce focal tissue acidosis by CO2 microdialysis in both models. For studies of mechanism, we alter neural function by injection/dialysis within the focal region of acidosis in the anesthetized rat. For studies of the RTN, we inhibit neurons reversibly by dialysis with muscimol, a GABA-A receptor agonist, in the chronic model. Central chemoreceptor physiology is significant; CO2 is a key component of the respiratory control system and CO2 retention in disease causes morbidity. Chemoreception and RTN function vary with arousal state, and thus are likely to be important in sleep disordered breathing, and the RTN is hypothesized to be an animal homologue for the arcuate nucleus, described as abnormal in SIDS victims.