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: 6202377
• 负责人: ANN C. BONHAM
• 金额: $ 23.31万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6202377
• 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，最后区神经元增强压力感受性反射， 交感神经系统的心肺反射调节。非常 关于中枢神经系统的部位、机制和药理学知之甚少 参与了扩增。我们的目标是找出 通路、机制和神经递质/神经调质， 最后神经元增强压力反射和心肺反射控制 交感神经活动我们认为，增强发生在早期， 孤束核水平的传入通路 最后区神经元增加了NTS神经元对 来自压力感受器或心肺传入的输入。我们展示 最后区和主动脉压力感受器电生理学 传入神经会聚到NTS中的相同神经元上，并以 便利的方式。最后区和迷走神经传入也是如此， 提示心肺最后区增大的基础 受体介导的交感神经抑制。我们建议将这项工作扩大到 测试以下具体假设：1.激活最后区 神经元增强心肺受体诱发的交感神经抑制 增加NTS细胞对心肺输入的反应性 受体。2.中枢最后区神经元的增强作用 压力感受器和心肺感受器传入的处理 NTS神经元的输入是通过从最后区到 从最后区到臂旁区的间接途径 核（PBN）和回到NTS。3.增强包括两个 孤束核内的多巴胺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测试。这些目标是：1. 确定最后区神经元的兴奋是否增强了 NTS中左心房受体敏感神经元对 激活左心房受体; 2.确定是否中断 PBN中的突触活动改变了最后区神经元的能力， 诱发来自NTS神经元的尖峰和/或增强那些 左心房感受器或压力感受器输入的孤束核神经元; 3. 确定PBN神经元是否接受来自区域的兴奋性输入， 最后肌向NTS发出传出投射; 4.确定 刺激最后区的神经递质/神经调质 神经元增强有髓左心房受体的反应性， NTS神经元对左心房受体激活敏感， 压力感受器敏感细胞对压力感受器激活; 5.确定 投射到NTS的最后区神经元（其中左心房 受体或压力感受器传入终止）或PBN的兴奋， 局部注射后叶加压素，这是牵连内的作用， 最后区以增强压力反射和心肺反射功能。