NEURAL SUBSTRATES FOR HYPOXIC EXCITATION OF BREATHING

尽管对呼吸的神经控制有广泛的兴趣， 细胞和分子机制，介导传入 外周化学感受器向脑干的传递 对呼吸神经元的了解仍然很少。 最近的研究， 然而，涉及特定类别的神经活性物质， 缺氧性呼吸反应的介质和调节剂. 神经轴的多个水平（颈动脉体、岩骨 神经节和髓质）。 例如，在外周， 颈动脉体中的肽能和多巴胺能成分， 岩神经节似乎对形成化学感受器至关重要， 放电 在中枢，化学感觉传入投射到区域 不仅含有速激肽和多巴胺， 已知调节呼吸输出的分子，包括鸦片制剂 肽和生长抑素。 然而，生理意义 岩神经节和延髓中的递质异质性， 以及大多数人的形态和生理机制 这些神经化学系统的相互作用是未知的。 处理这一 问题，拟议的研究旨在定义解剖，生理 以及突触相互作用的生化基质 在岩神经节的化学感受器传入神经元之间， 他们的外围和中心目标。 对颈动脉体的研究， 例如，将集中在多巴胺能和速激肽的作用， 肽能元件在调节化学感受功能中的应用 免疫细胞化学、超微结构和神经生理学方法。 在岩神经节，生化方法将确定的作用 缺氧和其他刺激在调节多巴胺能特性中的作用 颈动脉体传入神经 在咽束核（nTS）， 光学和电子显微镜方法将用于鉴定和 表征颈动脉的突触末梢和突触后靶点 躯体传入神经元 定量受体放射自显影将 用于关联特定的核内分布 受体亚型与颈动脉体传入纤维分布的关系。 这些发现将与生理和 关于速激肽肽作用的微离子电渗研究， 多巴胺和其他神经活性药物调节化学传入 输入Nts。 最后，神经解剖学和免疫细胞化学 技术将表征发射机特性， 新发现的颈动脉体传入神经亚群， 直接投射到尾侧延髓腹外侧区。 这些研究是更广泛的长期努力的一部分， 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.