NEURAL SUBSTRATES FOR HYPOXIC EXCITATION OF BREATHING

尽管人们对呼吸的神经控制很感兴趣， 介导传入的细胞和分子机制 外周化学感受器向脑干的传递 呼吸神经元仍然知之甚少。最近的研究表明， 然而，涉及特定类别的神经活性物质，如 缺氧呼吸反应的介体和调节物 多个水平的神经轴(颈动脉体部、岩部 神经节和髓质)。例如，在外周，速激宁 颈动脉小体和颈动脉小体中的肽能和多巴胺能成分 岩神经节似乎是形成化学感觉的关键 出院。在中枢，化学感觉传入投射到各区域 不仅含有速激肽和多巴胺，而且还含有其他 已知可调节呼吸输出的分子，包括阿片剂 多肽和生长抑素。然而，它的生理意义 在岩神经节和延髓的递质异质性， 以及大多数植物的形态和生理机制 这些神经化学系统的相互作用是未知的。要接近这一点 问题，拟议的研究旨在定义解剖学、生理学 以及作为突触相互作用基础的生化底物 岩神经节内化学感受性传入神经元与 他们的外围和中心目标。颈动脉小体的研究， 例如，将重点研究多巴胺能和速激肽的作用 调节化学感觉功能的肽能元件，使用 免疫细胞化学、超微结构和神经生理学方法。 在岩神经节中，生化方法将定义其作用 低氧和其他刺激在调节多巴胺能特性中的作用 颈动脉小体传入。在萨拉塔里核(NTS)， 将使用光学和电子显微镜方法来识别和 颈动脉突触终末和突触后靶点的特征 身体传入神经元。定量受体放射自显影将 被用来关联特定亚核的分布 受体亚型与颈动脉小体传入的分布。 这些发现将与生理学和 速激肽作用的微离子电泳法研究， 多巴胺等神经活性物质对化学传入的调节 对NTS的输入。最后，神经解剖和免疫细胞化学 技术将表征发送器属性，该属性由 新发现的颈动脉小体传入亚群 直接投射到延髓尾侧腹外侧区。 这些研究是更广泛的长期努力的一部分，旨在 了解呼吸控制的神经化学机制。

Despite widespread interest in the neural control of respiration, cellular and molecular mechanisms that mediate afferent transmission from peripheral chemoreceptors to brainstem respiratory neurons remain poorly understood. Recent studies, however, implicate specific classes of neuroactive substances as mediators and modulators of the hypoxic ventilatory response at multiple levels of the neuraxis (the carotid body, petrosal ganglion and medulla). In the periphery, for example, tachykinin peptidergic and dopaminergic elements in the carotid body and petrosal ganglion appear to be critical for shaping chemosensory discharge. Centrally, chemosensory afferents project to regions that contain not only tachykinins and dopamine, but also other molecules known to modulate respiratory output, including opiate peptides and somatostatin. However, the physiologic significance of transmitter heterogeneity in the petrosal ganglion and medulla, and the morphologic and physiologic mechanisms by which most of these neurochemical systems interact are unknown. To approach this issue, the proposed research aims to define anatomic, physiologic and biochemical substrates that underlie synaptic interactions between chemoreceptor afferent neurons in the petrosal ganglion and their peripheral and central targets. Studies in the carotid body, for example, will focus on the role of dopaminergic and tachykinin peptidergic elements in modulating chemosensory function, using immunocytochemical, ultrastructural and neurophysiologic methods. In the petrosal ganglion, biochemical methods will define the role of hypoxia and other stimuli in regulating dopaminergic traits in carotid body afferents. In the nucleus tractus salitarius (nTS), light and electron microscopic methods will be used to identify and characterize synaptic terminals and postsynaptic targets of carotid body afferent neurons. Quantitative receptor autoradiography will be used to correlate the subnuclear distribution of specific receptor subtypes with the distribution of carotid body afferents. These findings will be correlated with physiologic and microiontophoretic studies on the role of tachykinin peptides, dopamine and other neuroactive agents in regulating chemoafferent inputs to Nts. Finally, neuroanatomic and immunocytochemical techniques will characterize transmitter properties expressed by a newly discovered subpopulation of carotid body afferents that project directly to the region of the caudal ventrolateral medulla. These studies are part of a broader long-range effort aimed at understanding neurochemical mechanisms of respiratory control.