Oxytocin enhances afferent synaptic transmission within the NTS.

描述（由申请人提供）：颅传入神经元是延髓反射通路的第一步，是孤束核（NTS）的突触。由于延髓反射通路而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是重要的。下丘脑室旁核（PVN）通过向NTS的肽能投射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中合成并包含在终止于NTS内的轴突中。心血管调节的研究表明，在一定的生理条件下，孤束核可释放AVP和OT，改变压力感受性反射。OT作用于NTS减慢心脏并降低动脉压，这一作用与压力反射增强一致;然而，这些作用的机制仍不清楚。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感受器反射。这项建议将测试是否催产素增强颅内脏传入/ NTS突触传递使用解剖学和电生理学的方法相结合。我将使用一个包含孤束和NTS的体外延髓脑切片，用膜片钳记录技术测量单个NTS神经元内的电流和突触传递。孤束的局部电刺激在NTS神经元中产生用于识别二级（直接）突触连接的突触反应。我也将研究一个特殊的延髓反射途径，在心血管功能的控制中很重要。具体来说，我将测试，如果催产素增强突触传递到NTS神经元接受压力感受性传入输入和投射到尾侧腹外侧髓质（CVLM）。将使用荧光神经元示踪剂完成压力感受性传入群体和投射到CVLM的NTS神经元的鉴定。解剖示踪结合全细胞电生理技术的组合将允许测试以下特定的假设：目的1）催产素是否增强传入神经递质传递到二级NTS神经元？目的2）催产素是否增强压力感受性二级NTS神经元的突触传递？目的3）催产素是否增强ST段传导至延髓尾侧腹外侧区？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。

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.