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: 7446726
• 负责人: James Henry Peters
• 金额: $ 5.13万
• 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 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7446726
• 关键词: Afferent Neurons; Anatomy; Area; Arginine; Argipressin; Autonomic nervous system; Axon; Baroreflex; Blood Vessels; Brain; Brain Stem; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cell Nucleus; Cells; Cephalic; Chromosome Pairing; Communication; Condition; Electric Stimulation; Glutamates; Heart; Heart Rate; Homeostasis; Hypothalamic structure; In Vitro; Intervention; Lateral; Localized; Lung; Measures; Neuraxis; Neurons; Neuropeptides; Neurotransmitters; Nucleus solitarius; Numbers; Organ; Output; Oxytocin; Pathway interactions; Physiological; Population; Positioning Attribute; Preparation; Pressoreceptors; Presynaptic Terminals; Prosencephalon; Range; Reflex action; Reflex control; Regulation; Research; Site; Slice; Synapses; Synaptic Transmission; Techniques; Testing; Thinking; Tracer; Training; Vasopressins; 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（申请人提供）：颅传入神经元是髓质反射通路的第一步，是孤立束核（NTS）的突触。髓质反射通路产生的反射控制在包括心血管功能在内的许多生理参数的调节中起重要作用。下丘脑的室旁核（PVN）通过肽能投射到NTS，帮助协调这些反射功能。两种原型神经肽，精氨酸加压素（AVP）和催产素（OT），在PVN中合成，并包含在NTS终止的轴突中。心血管调节的研究表明，在一定的生理条件下，AVP和OT在NTS中释放并改变压力感受器反射。在NTS中作用的OT减慢心脏和降低动脉压，这一作用与气压反射增强一致；然而，这些影响的机制仍然未知。我的总体假设是，催产素通过促进NTS内的压力感受器传入突触传递来增强压力反射。本研究将结合解剖学和电生理学的方法来测试催产素是否能增强颅内脏传入/ NTS突触的传递。我将使用体外脑髓质切片，其中包含孤立束和NTS，并使用膜片钳记录技术来测量单个NTS神经元内的电流和突触传递。孤立束局部电刺激在NTS神经元中产生突触反应，用于识别二级（直接）突触连接。我还将研究在心血管功能控制中重要的特定髓质反射通路。具体来说，我将测试催产素是否会增强NTS神经元的突触传递，这些神经元接受压力感受性传入输入并投射到尾侧腹侧髓质（CVLM）。使用荧光神经元示踪剂可以识别压力感受性传入群体和投射到CVLM的NTS神经元。解剖示踪与全细胞电生理技术的结合将允许测试以下特定假设：目的1)催产素是否增强传入谷氨酸能传递到二阶NTS神经元？目的2)催产素是否增强突触传递到压力感受性二阶NTS神经元？目的3)催产素是否增强ST向尾侧腹外髓质的传递？这项研究将扩大我们对自主反射控制的理解，心血管系统是如何调节的，并可能为心血管疾病的治疗干预和治疗提供建议。