Central Interaction of Baroreceptor & Somatic Afferents

压力感受器的中枢相互作用

• 批准号: 6909874
• 负责人: Jeffrey Thomas Potts
• 金额: $ 18.38万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6909874
• 关键词: GABA receptor; baroreceptors; baroreflex; carotid sinus; electrophysiology; immunocytochemistry; laboratory rat; microelectrodes; neural information processing; neural plasticity; neuroanatomy; neurons; neurophysiology; solitary tract nucleus; somatic afferent nerve; striated muscles; synapses

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.

描述（由申请人提供）：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感受性反射的中枢机制尚未完全清楚。 运动时动脉压力感受器和骨骼肌感受器传入被刺激，并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团，其处理这些输入并将其传递到控制自主运动流出的其他髓核和髓上核团。 在该奖项的最初任期内的先前工作，沿着与此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SPergic回路来抑制动脉压力感受器信号传导。 本申请的具体目的是：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感受器反射控制中的作用; 2）表征功能鉴定的单单位NTS神经元的突触反应，并确定GABA能和Spergic受体对神经元和网络兴奋性的贡献;（3）确定骨骼肌的无害性和有害性反馈对动脉压力感受性反射功能的作用。 为了实现这些目标，将使用生理学范例在年轻成年大鼠中使用原位未麻醉的动脉灌注工作心-脑干制备物和体内未麻醉的去大脑制备物来激活动脉压力感受器和收缩敏感性/伤害感受性骨骼肌受体。 GABA能和SPergic机制在NTS中的作用将通过GABA受体和神经激肽-1受体的选择性激动剂和拮抗剂的中央显微注射，以及这些化合物的皮可喷射直接到功能鉴定的单单位NTS神经元使用多管微电极检查。 这些研究的结果将提供新的信息，NTS神经元的作用，在感觉处理的神经反馈动脉压力感受器和骨骼肌受体。 这些知识将扩大我们的理解，压力感受器和躯体传入神经之间的中枢相互作用的水平的NTS，并将提供一个细胞的基础上，以解释突触机制的压力反射重置在运动过程中。