AREA POSTREMA MODULATION OF AFFERENT INPUT FROM BARORECEPTOR AND ATRIAL RECEPTORS

众所周知，最后区神经元增强压力感受性反射和 交感神经系统的心肺反射调节。非常 对中枢神经系统的部位、机制和药理学知之甚少 参与了扩容。我们的目标是确定中央 通路、机制和神经递质/神经调节剂 后叶神经元增强压力反射和心肺反射的控制 交感神经活动。我们认为，增强发生在早期 孤束核(NTS)水平的传入通路 延髓后区神经元增加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 电生理上最后区和主动脉压力感受器 传入神经元汇聚到NTS中的相同神经元上，并在 以促进的方式。最后区和迷走神经传入也是如此， 为心肺后区扩大提供依据 受体介导的交感神经抑制。我们建议将这项工作扩大到 检验以下具体假设：1.最后区激活 神经元增强心肺受体引起的交感神经抑制 提高NTS细胞对心肺输入的反应性 感受器。2.中央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神经元的传入是通过从最后区到 NTS和从最后区到臂旁的间接途径 核团(PBN)，回到NTS。3.增强涉及到两者 孤束核内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身上进行了测试。这些目标是：1. 确定兴奋最后区神经元是否会增加 孤束核内左房受体敏感神经元的反应性 激活左房感受器；2.确定是否阻断 PBN中的突触活动改变最后区神经元的能力 诱发NTS神经元的棘波和/或增强这些神经元的处理 左房感受器或压力感受器传入的NTS神经元； 确定从脑区接受兴奋性输入的PBN神经元 后遗症向NTS发出传出投射；4.确定 神经递质/神经调质(S)，刺激最后区 神经元增强有髓左心房感受器的反应性 NTS神经元对左房感受器兴奋的敏感性 压力感受器敏感细胞对压力感受器的激活；5.确定 最后区神经元是否投射到NTS(左房 受体或压力感受器传入终止)或至PBN的兴奋 局部注射加压素，这与在脑内的作用有关 最后区，增强压力反射和心肺反射功能。

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.