Oxytocin enhances afferent synaptic transmission within the NTS.

催产素增强 NTS 内的传入突触传递。

• 批准号: 7643912
• 负责人: James Henry Peters
• 金额: $ 3.63万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2010-01-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7643912
• 关键词: Afferent Neurons; Anatomy; Area; Argipressin; Autonomic nervous system; Axon; Baroreflex; Blood Vessels; Brain; Brain Stem; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cell Nucleus; Cells; Cephalic; Communication; Electric Stimulation; Glutamates; Heart; Heart Rate; Homeostasis; Hypothalamic structure; In Vitro; Intervention; Lateral; Lung; Measures; Neuraxis; Neurons; Neuropeptides; Neurotransmitters; Nucleus solitarius; Organ; Output; Oxytocin; Pathway interactions; Physiological; Population; Positioning Attribute; Preparation; Pressoreceptors; Presynaptic Terminals; Prosencephalon; Reflex action; Reflex control; Regulation; Research; Site; Slice; Synapses; Synaptic Transmission; Techniques; Testing; Tracer; Training; Visceral Afferents; autonomic reflex; gamma-Aminobutyric Acid; paraventricular nucleus; patch clamp; postsynaptic; pressure; presynaptic; receptor; research study; response; transmission process

DESCRIPTION (provided by applicant): Cranial afferent neurons are the first step in medullary reflex pathways and synapse at the nucleus of the solitary tract (NTS). Reflex control produced as a result of medullary reflex pathways is important in the regulation of many physiological parameters including cardiovascular function. The paraventricular nucleus (PVN) of the hypothalamus helps to coordinate these reflex functions through peptidergic projections to the NTS. Two prototypic neuropeptides, arginine vasopressin (AVP) and oxytocin (OT), are synthesized in the PVN and contained in axons terminating within NTS. Studies of cardiovascular regulation suggest that AVP and OT are released in NTS under certain physiological conditions and alter the baroreceptor reflex. OT acting in NTS slows the heart and decreases arterial pressure, an action consistent with an enhancement of the baroreflex; the mechanisms of these effects, however, remain unknown. My global hypothesis is that oxytocin enhances the baroreflex by facilitating baroreceptor afferent synaptic transmission within NTS. This proposal will test whether oxytocin enhances cranial visceral afferent / NTS synaptic transmission using a combination of anatomical and electrophysiological approaches. I will use an in vitro medullary brain slice, which contains the solitary tract and the NTS, with patch-clamp recording techniques to measure electrical current and synaptic transmission within a single NTS neuron. Localized electrical stimulation of the solitary tract produces synaptic responses in NTS neurons that are used to identify second order (direct) synaptic connections. I will also investigate a specific medullary reflex pathway important in the control of cardiovascular function. Specifically, I will test if oxytocin enhances synaptic transmission to NTS neurons receiving baroreceptive afferent inputs and projecting to the caudal ventro-lateral medulla (CVLM). The Identification of baroreceptive afferent populations and NTS neurons with projections to the CVLM will be accomplished using fluorescent neuronal tracers. The combination of anatomic tracing combined with whole cell electrophysiological techniques will allow for the test of the following specific hypotheses: Aim 1) Does oxytocin enhance afferent glutamatergic transmission to second-order NTS neurons? Aim 2) Does oxytocin enhance synaptic transmission to baroreceptive second-order NTS neurons? Aim 3) Does oxytocin enhance ST transmission to the caudal ventrolateral medulla? This research will expand our understanding of autonomic reflex control, how the cardiovascular system is regulated and may suggest sites for therapuetic intervention and treatment of cardiovascular disease.

描述（由申请人提供）：颅神经元是髓样途径的第一步和孤立区核（NTS）核的突触。由于髓质反射途径而产生的反射控制对于调节包括​​心血管功能在内的许多生理参数的调节很重要。下丘脑的室室核（PVN）有助于通过肽固定的投影对NTS来协调这些反射功能。在PVN中合成了两种原型神经肽，精氨酸加压素（AVP）和催产素（OT），并包含在NTS内终止的轴突中。心血管调节的研究表明，AVP和OT在某些生理条件下在NTS中释放并改变了压力感受器反射。在NT中作用的OT会减慢心脏并降低动脉压，这是一种与降压反射增强的作用。但是，这些作用的机制仍然未知。我的全球假设是，催产素通过促进NTS内的压力感受器传入的突触传播来增强压力反射。该建议将测试催产素是否通过解剖学和电生理方法的组合来增强颅内脏传入 / NTS突触传播。我将使用包含孤立区和NTS的体外髓质脑切片，并带有贴片钳记录技术来测量单个NTS神经元内的电流和突触传播。孤立道的局部电刺激会在NTS神经元中产生突触反应，这些神经元用于识别二阶（直接）突触连接。我还将研究在控制心血管功能中重要的特定髓质反射途径。具体而言，我将测试催产素是否增强了接收压力感应传入输入并投射到尾腹腹侧髓质（CVLM）的NTS神经元的突触传播。使用荧光神经元示踪剂来完成对带有CVLM投影的压力感受传入群体和NTS神经元的鉴定。解剖跟踪与全细胞电生理技术结合的结合将允许测试以下特定假设：目标1）催产素是否可以增强传入的谷氨酸能传播到二阶NTS神经元？目的2）催产素会增强对压力感受的二阶NTS神经元的突触传播吗？目标3）催产素会增强向尾腹外侧髓质的传播吗？这项研究将扩大我们对自主反射控制的理解，如何调节心血管系统，并可能建议用于治疗干预和治疗心血管疾病的部位。