Oxytocin enhances afferent synaptic transmission within the NTS.

描述(申请人提供)：颅脑传入神经元是延髓反射通路和孤束核(NTS)突触的第一步。由髓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着重要作用。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。精氨酸加压素(AVP)和催产素(OT)是在下丘脑室旁核合成的两种典型神经肽，存在于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，AVP和OT在NTS内释放，并改变压力感受器反射。OT作用于NTS可使心脏减慢并降低动脉压，这一作用与增强压力感受器反射相一致；然而，这些影响的机制仍不清楚。我的总体假设是，催产素通过促进压力感受器传入突触在NTS内的传递来增强压力感受性反射。这项建议将结合解剖学和电生理学方法，测试催产素是否能增强脑内脏传入/NTS突触传递。我将使用包含孤束和NTS的体外延髓脑片，结合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。孤束的局部电刺激在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一种特殊的髓质反射途径。具体地说，我将测试催产素是否增强了到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延髓腹外侧区(CVLM)。向CVLM投射的压力感受性传入群体和NTS神经元的识别将使用荧光神经元示踪剂完成。解剖示踪和全细胞电生理技术的结合将允许检验以下特定的假设：目的1)催产素是否增强了传入的谷氨酸能传递到二阶NTS神经元？目的2)催产素是否增强了压力感受性二阶NTS神经元的突触传递？目的3)催产素是否增强ST向延髓尾侧腹外侧区的传递？这项研究将扩大我们对自主神经反射控制的理解，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.