AREA POSTREMA MODULATION OF AFFERENT INPUT FROM BARORECEPTOR AND ATRIAL RECEPTORS

来自压力感受器和心房感受器的传入输入的后区调制

• 批准号: 6110337
• 负责人: ANN C. BONHAM
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-14 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6110337
• 关键词: afferent nerve; area postrema; arginine vasopressin; baroreceptors; electrophysiology; laboratory rabbit; neural inhibition; neural transmission; neuroanatomy; neurotransmitters; parabrachial nucleus; receptor; solitary tract nucleus; sympathetic nervous system

It is well known that area postrema neurons augment baroreflex and cardiopulmonary reflex regulation of the sympathetic nervous system. Very little is known regarding the CNS sites, mechanisms, and pharmacology involved in the augmentation. Our goal is to identify the central pathways, mechanisms, and neurotransmitter/neuromodulators whereby area postrema neurons augment baroreflex and cardiopulmonary reflex control of sympathetic nerve activity. We propose that augmentation occurs early in the afferent pathways at the level of nucleus tractus solitarius (NTS) where area postrema neurons increase the sensitivity of NTS neurons to inputs from baroreceptor or cardiopulmonary afferents. We showed electrophysiologically that area postrema and aortic baroreceptor afferents converge onto the same neurons in the NTS and interact in a facilitatory manner. Same was true for area postrema and vagal afferents, suggesting a basis for area postrema augmentation of cardiopulmonary receptor-mediated sympathoinhibition. We propose to extend this work to test the following specific hypotheses: 1. Activation of area postrema neurons augments cardiopulmonary receptor-evoked sympathoinhibition increasing the responsiveness of NTS cells to input from cardiopulmonary receptors. 2. Augmentation by area postrema neurons of the central processing of both baroreceptor and cardiopulmonary receptor afferent input by NTS neurons is mediated by a direct route from area postrema to the NTS and by an indirect route from area postrema to the parabrachial nucleus (PBN) and back to the NTS. 3. Augmentation involves both glutamatergic and noradrenergic synapses in NTS. Hypotheses will be tested in pentobarbital-anesthetized rabbits. These aims are: 1. determine whether excitation of area postrema neurons augments the responsiveness of left atrial receptor-sensitive neurons in the NTS to activate the left atrial receptors; 2. determine whether interruption of synaptic activity in PBN alters the ability of area postrema neurons to evoke spikes from NTS neurons and/or to augment the processing by those NTS neurons of either left atrial receptor or baroreceptor input; 3. determine whether PBN neurons that receive excitatory inputs from area postrema send efferent projections to the NTS; 4. determine the neurotransmitter/neuromodulator(s) by which stimulation of area postrema neurons augment responsiveness of myelinated left atrial receptor- sensitive NTS neurons to left atrial receptor activation and of baroreceptor-sensitive cells to baroreceptor activation; 5. determine whether area postrema neurons which project to the NTS (where left atrial receptor or baroreceptor afferents terminate) or to the PBN are excited by local injections of vasopressin, which is implicated at acting within the area postrema to augment baroreflex and cardiopulmonary reflex function.

众所周知，区域postrema神经元增强Baroreflex和 交感神经系统的心肺反射调节。非常 关于中枢神经系统地点，机制和药理学知之甚少 参与增强。我们的目标是确定中央 途径，机制和神经递质/神经调节剂区域 Postrema神经元增强Baroreflex和心肺反射对照 交感神经活动。我们建议增强发生在早期 核核核（NTS）核水平的传入途径 区域postrema神经元增加了NTS神经元对 来自压力感受器或心肺传入的输入。我们展示了 从电生理上讲，该区域Postrema和主动脉压力感受器 传入在NTS中收敛到相同的神经元，并在A中相互作用 促进方式。区域Postrema和迷走神经传入也是如此， 为心肺增强区域增强区域的基础 受体介导的交感神经抑制作用。我们建议将这项工作扩展到 测试以下特定假设：1。激活面积Postrema 神经元增强心肺受体诱发的交感神经抑制作用 增加NTS细胞对来自心肺输入的反应性 受体。 2。中央区域postrema神经元的增强 对压力感受器和心肺受体传入的处理 NTS神经元的输入是由从区域Postrema到的直接路线介导的 NTS以及从区域Postrema到parabrachial的间接路线 核（PBN）并回到NTS。 3。增强涉及两者 NTS中的谷氨酸能和去甲肾上腺素能突触。假设将是 在戊巴比妥 - 麻醉的兔子中进行了测试。这些目标是：1。 确定兴奋区域神经元是否会增加 NTS中左心房受体敏感神经元的反应性 激活左心房受体； 2。确定是否中断 PBN中的突触活动改变了区域postrema神经元的能力 引起NTS神经元的尖峰和/或增加那些人的处理 左心房受体或压力感受器输入的NTS神经元； 3。 确定是否从区域接收兴奋性输入的PBN神经元 Postrema向NTS发送传出预测； 4。确定 神经递质/神经调节剂（S），该​​区域刺激面积 神经元增强髓鞘的反应性左心房受体 - 敏感的NTS神经元左心房受体激活和 压力感受器敏感的细胞对压力感受器的激活； 5。确定 区域postrema神经元是否向NTS发射 受体或压力感受器传入终止）或对PBN的激发 局部注射加压素，这与在 区域postrema增强Baroreflex和心肺反射功能。