HYPOTHALAMIC CONTROL OF THE CARDIORESPIRATORY SYSTEMS

下丘脑对心肺系统的控制

• 批准号: 3355065
• 负责人: TONY G WALDROP
• 金额: $ 11.57万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1995-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3355065
• 关键词: baroreceptors; brain mapping; cardiovascular system; cats; cerebral ischemia /hypoxia; chemoreceptors; efferent nerve; electrophysiology; experimental brain lesion; heart innervation; hypothalamus; microinjections; neural conduction; neural information processing; neuropharmacology; neurotransmitters; phrenic nerve; pulmonary stretch receptors; respiration regulatory center; respiratory function; respiratory reflex; single cell analysis; spinal cord; spontaneous hypertensive rat; stretch reflex; sympathetic nervous system; tissue /cell culture; voltage /patch clamp

The long-term goal of research in this laboratory is to elucidate the role of caudal hypothalamic neurons in regulating cardiorespiratory activity. The specific aims are to: 1) provide evidence for the physiological function of caudal hypothalamic neurons; 2) identify stimuli which alter the discharge of identified neurons; 3) determine projections of caudal hypothalamic neurons to lower brainstem and spinal cord sites; and 4) examine possible contributions of caudal hypothalamic neurons to elevated pressure present in spontaneously hypertensive rats. Both in vivo and in vitro preparations will be used to address these aims. The first set of experiments will be performed in anesthetized cats. Computer signal averaging techniques will be utilized to correlate basal discharge frequency of hypothalamic neurons with the cardiac cycle, sympathetic nerve activity and/or phrenic nerve activity. In addition, single unit responses of these neurons to various stimuli (hypoxia, hypercapnia, baroreceptor activation, pulmonary stretch receptor stimulation) will be recorded. An attempt will then be made to determine the axonal projection of all neurons studied using antidromic activation and mapping techniques. An in vitro rat brain slice preparation will be utilized to evaluate the direct effects of hypoxia and hypercapnia upon caudal hypothalamic neurons. Whole cell patch recordings will be performed in the brain slice experiments; retrograde transport of rhodamine microbeads will be used in an attempt to determine projection sites of studied neurons. In vivo experiments will also be undertaken in spontaneously hypertensive rats (SHR) to determine if neuronal activity in the caudal hypothalamus is altered relative to that of normotensive rats. Computer averaging techniques will determine the proportion of caudal hypothalamic neurons which have a cardiac and/or sympathetic discharge. Each neuron will also be tested for a response to baroreceptor stimulation. In a final set of experiments, characteristics of hypothalamic neurons from SHR rats will be compared to those of normotensive rats in a brain slice preparation. Comparisons will be made between neurons from young and mature spontaneously hypertensive rats and with normotensive controls. The results of these studies may offer insight into neurological abnormalities contributing to the origination and/or maintenance of high blood pressure and altered cardiorespiratory reflexes.

该实验室研究的长期目标是阐明其作用 下丘脑尾部神经元在调节心肺活动中的作用。 具体目标是：1）为生理学提供证据 下丘脑尾部神经元的功能； 2）识别改变的刺激 已识别神经元的放电； 3) 确定尾部的投影 下丘脑神经元位于脑干和脊髓下部；和 4) 检查尾部下丘脑神经元对升高的可能贡献 自发性高血压大鼠中存在压力。 无论是体内还是体内 体外制剂将用于实现这些目标。 第一组 实验将在麻醉猫身上进行。 电脑信号 将利用平均技术来关联基础放电 下丘脑神经元频率与心动周期、交感神经的关系 活动和/或膈神经活动。 此外，单个单元响应 这些神经元对各种刺激（缺氧、高碳酸血症、压力感受器 激活、肺牵张感受器刺激）将被记录。 一个 然后将尝试确定所有神经元的轴突投影 使用逆向激活和绘图技术进行研究。 体外 大鼠脑切片制备将用于评估直接效果 下丘脑尾部神经元的缺氧和高碳酸血症。 全细胞 脑切片实验中将进行补丁记录； 将使用罗丹明微珠的逆行运输来尝试 确定所研究神经元的投射位点。 体内实验将 也可在自发性高血压大鼠 (SHR) 中进行以确定是否 下丘脑尾部的神经元活动相对于 血压正常的大鼠。 计算机平均技术将确定 下丘脑尾部神经元具有心脏和/或 交感神经放电。 每个神经元也将被测试以响应 压力感受器刺激。 在最后一组实验中，特征 SHR 大鼠的下丘脑神经元将与 正常血压大鼠的脑切片制备。 将会进行比较 年轻和成熟自发性高血压大鼠的神经元之间 血压正常控制。 这些研究的结果可能会提供见解 导致神经系统异常的起源和/或 维持高血压和改变心肺反射。