Central Interaction of Baroreceptor & Somatic Afferents

描述（申请人提供）：运动改变动脉压力感受器反射功能。然而，在运动过程中调节动脉压力反射的主要机制尚不完全清楚。运动时，动脉压力感受器和骨骼肌感受器传入神经受到刺激，将感觉信息传递到孤束核。NTS是哺乳动物脑干中的主要感觉核，处理并将这些输入传递给控制自主运动流出的其他髓核和髓上核。在该奖项最初任期内的前期工作以及竞争性更新的初步数据表明，骨骼肌受体的突触输入通过激活NTS中的局部GABAergic和SPergic回路来抑制动脉压力受体信号。该应用的具体目的是：1)确定gaba能和SPergic机制在迷走神经和交感神经运动活动的中枢压力反射控制中的作用；2)表征功能识别的单个NTS神经元的突触反应，并确定GABAergic和SPergic受体对神经元和网络兴奋性的贡献；3)确定来自骨骼肌的无害和有害反馈对动脉压力反射功能的作用。为了实现这些目标，将使用生理范式来激活动脉压力感受器和收缩敏感/伤害性骨骼肌感受器，在年轻成年大鼠中使用原位未麻醉，动脉灌注的工作心脏-脑干准备和体内未麻醉的脱脑准备。GABA受体和神经激肽-1受体的选择性激动剂和拮抗剂，以及使用多管微电极将这些化合物直接微射到功能鉴定的单单元NTS神经元上，研究GABA能和SPergic机制在NTS中的作用。这些研究结果将为NTS神经元在动脉压力感受器和骨骼肌感受器神经反馈的感觉加工中的作用提供新的信息。这些知识将扩展我们对NTS水平的压力感受器和躯体传入之间的中心相互作用的理解，并将为解释运动过程中压力反射重置的突触机制提供细胞基础。

DESCRIPTION (provided by applicant): Exercise alters arterial baroreceptor reflex function. However, the central mechanisms that modulate the arterial baroreflex during exercise are not completely understood. Arterial baroreceptor and skeletal muscle receptor afferents are stimulated during exercise and transmit sensory information to the nucleus tractus solitarii (NTS). The NTS is the major sensory nucleus in the mammalian brainstem that processes and relays these inputs to other medullary and supra-medullary nuclei controlling autonomic motor outflow. Previous work during the initial tenure of this award, along with preliminary data for this competitive renewal, has demonstrated that synaptic input from skeletal muscle receptors inhibits arterial baroreceptor signaling by activating local GABAergic and SPergic circuits in the NTS. The specific aims for this application are: 1) to determine the role GABAergic and SPergic mechanisms on central baroreflex control of vagal and sympathetic motor activity; 2) to characterize the synaptic responses of functionally-identified single-unit NTS neurons and to determine the contribution of GABAergic and SPergic receptors on neuronal and network excitability; and 3) to determine the role of innocuous and noxious feedback from skeletal muscle on arterial baroreflex function. To accomplish these aims, physiological paradigms will be used to activate arterial baroreceptors and contraction-sensitive / nociceptive skeletal muscle receptors using an in situ unanesthetized, arterially perfused working heart-brainstem preparation and an in vivo unanesthetized decerebrate preparation in young adult rats. The role of GABAergic and SPergic mechanisms in the NTS will be examined by central microinjections of selective agonists and antagonists for GABA receptors and neurokinin-1 receptors, as well as picoejection of these compounds directly onto functionally identified single-unit NTS neurons using multibarrel microelectrodes. Results from these studies will provide new information regarding the role of NTS neurons in the sensory processing of neural feedback from arterial baroreceptors and skeletal muscle receptors. This knowledge will extend our understanding of the central interaction between baroreceptor and somatic afferents at the level of the NTS and will provide a cellular basis to explain the synaptic mechanisms underlying baroreflex resetting during exercise.