Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways

项目摘要 压力反射是一种稳态反馈途径，负责维持稳定的血液流向大脑。 压力感受器信号传递到孤束核，然后传递到延髓尾侧腹外侧区 （CVLM）。CVLM将兴奋性和GABA能抑制性投射发送到头侧腹外侧核 延髓（RVLM），其反过来又为脊髓中的节前交感神经元提供关键输入 控制交感神经活动压力反射通路是多突触的，具有相对长的潜伏期， 并且仅是反应性的，响应于先前的心血管疾病而调节血管收缩和心率。 例如血压（BP）的变化。前庭交感神经反射（VSR） 介导主动、直接和快速的BP调节，在发病时启动体内血液重新分布， 运动或姿势调整，以确保一致的脑灌注，无论头部 位置VSR由来自前庭终末器官的输入触发，前庭终末器官将信号传递到前庭终末器官中的神经元。 投射到CVLM和/或RVLM的尾侧前庭核（VNc）。通过VNc激活该通路 引起交感神经活动和血压的变化。我们最近发现，有两个分支的 VSR，一种是GABA能和脓毒性抑制性的，另一种是脓毒性兴奋性的， 神经过敏。拟议研究的目标是确定这两个特定的连接 化学解剖方面的VSR使用一种新的方法来激活个别终末器官。测试整体 假设刺激引起的BP变化的方向反映了差异激活， VSR的这两个主要分支的连接和突触学。该项目利用了空间 脉冲红外激光刺激前庭终末器官的特异性， 单个受体区域。我们将检验局灶性刺激局限于椭圆囊或球囊的假设 激活特定的化学解剖学定义的VSR神经元亚型， 在VNC内，主要投射到RVLM或CVLM。此外，我们还将研究 VSR介导的椭圆囊、囊状和后半规管联合激活对BP的影响。 将进行超微结构研究以确认该通路的详细解剖结构。总的来说，这个项目 阐述了VSR反应的解剖学基础，是建立实用性和有效性的基础 红外激光刺激作为下一代前庭自主神经紊乱的治疗方法， 神经源性直立性低血压和不耐受。

PROJECT SUMMARY The baroreflex is a homeostatic feedback pathway responsible for maintaining stable blood flow to the brain. Baroreceptor signals are conveyed to the solitary nucleus and then to the caudal ventrolateral medulla (CVLM). The CVLM sends both excitatory and GABAergic inhibitory projections to the rostral ventrolateral medulla (RVLM), which in turn provides the key input to preganglionic sympathetic neurons in the spinal cord that control sympathetic nerve activity. The baroreflex pathway is polysynaptic, has a relatively long latency, and is solely reactive, modulating vasoconstriction and heart rate in response to a prior cardiovascular vicissitude such as a change in blood pressure (BP). In contrast, the vestibulo-sympathetic reflex (VSR) mediates proactive, direct and rapid BP modulation, initiating blood redistribution in the body at the onset of movement or a postural adjustment in order to assure consistent cerebral perfusion regardless of head position. The VSR is triggered by input from the vestibular end organs, which convey signals to neurons in the caudal vestibular nuclei (VNc) that project to CVLM and/or RVLM. Activation of this pathway through VNc causes changes in sympathetic nerve activity and BP. We have recently found that there are two limbs of the VSR, one that is GABAergic and putatively inhibitory, and another that is putatively excitatory and glutamatergic. The goal of the proposed research is to determine the specific connectivity of these two chemoanatomic facets of the VSR using a novel approach to activate individual end organs. testing the overall hypothesis that the direction of BP change resulting from stimulation reflects the differential activation, connectivity and synaptology of these two main limbs of the VSR. The project takes advantage of the spatial specificity of pulsed infrared laser stimulation of the vestibular end organs in order to discretely activate individual receptor regions. We will test the hypotheses that focal stimulation restricted to the utricle or saccule activates specific chemoanatomically-defined subtypes of VSR neurons that are topographically segregated within the VNC and project primarily to either RVLM or CVLM. In addition, we will investigate the effects of combined utricular, saccular and posterior semicircular canal activation on BP mediated by the VSR. Ultrastructural studies will be conducted to confirm the detailed anatomy of this pathway. Overall, this project addresses the anatomical bases for VSR responses, and is foundational for establishing the utility and efficacy of infrared laser stimulation as a next-generation treatment for vestibulo-autonomic disorders including neurogenic orthostatic hypotension and intolerance.