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，运动中调节动脉压力感受器反射的中枢机制还不完全清楚。运动时刺激动脉压力感受器和骨骼肌感受器传入，将感觉信息传递到孤束核(NTS)。NTS是哺乳动物脑干中的主要感觉核，负责处理这些信息并将其传递给其他控制自主运动流出的延髓和髓上核团。在该奖项最初任期内的先前工作，以及这次竞争性更新的初步数据，已经证明来自骨骼肌受体的突触输入通过激活NTS中的局部GABA能和SPer能回路来抑制动脉压力感受器信号。这一应用的具体目的是：1)确定GABA能和S能在中枢压力反射控制迷走神经和交感神经运动活动中的作用；2)表征功能识别的单单位NTS神经元的突触反应，并确定GABA和S能受体对神经元和网络兴奋性的贡献；以及3)确定骨骼肌无害和伤害性反馈对动脉压力反射功能的作用。为了实现这些目标，生理范式将被用来激活动脉压力感受器和收缩敏感/伤害性骨骼肌受体，使用原位未麻醉的、动脉灌流的工作心脏-脑干制剂和体内未麻醉的去大脑制剂。GABA能和S能机制在NTS中的作用将通过中枢微量注射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喷射到功能识别的单单位NTS神经元上来检验。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的神经反馈的感觉处理中的作用提供新的信息。这一认识将扩展我们对压力感受器和躯体传入之间在NTS水平的中枢相互作用的理解，并将为解释运动中压力感受性反射重置的突触机制提供细胞学基础。

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.