CEREBELLUM--ROLE IN THE CHEMICAL CONTROL OF BREATHING

描述（申请人摘要）：我们实验室的先前研究， 其他人已经证明，小脑，特别是嘴侧 小脑顶核（FNR）在呼吸反应中起易化作用 尤其是严重的高碳酸血症迄今为止， 小脑参与高碳酸血症的呼吸反应 未知利用体内和体外（细胞培养）的最新证据 技术提出了一些FNR神经元可能是化学敏感的可能性。 因此，我们假设小脑调节脑电的能力， 对酸性刺激（CO2/H+）的反应至少部分是， 这归因于FNR化学敏感神经元的激活。此外，我们将 研究突触投射和神经递质利用这些 化学敏感神经元来调节呼吸反应。具体的目标是 1）确定呼吸系统中FNR神经元的独特参与， 与其他小脑深部核团相比，对高碳酸血症的反应; 2）验证 的存在、位置和电生理特征 FNR内负责呼吸增强的化学敏感神经元 局灶性组织酸化; 3）确定FNR的突触连接 这种FNR介导的呼吸反应所必需的神经元;以及4）证明 谷氨酸和/或γ-氨基丁酸（GABA）的参与作为潜在的 在这个FNR传出通路的神经递质。这一建议将阐明 小脑如何促进对CO2/H+刺激的呼吸反应 通过使用多学科方法（电生理学、免疫组织化学 药理学）。结果将大大拓宽我们的常识 参与呼吸的化学控制和增强 我们对中枢介导的神经化学机制的理解 呼吸对生理压力的反应，如运动。也许更 令人兴奋的是一个新兴的概念，小脑可能更参与 在规划和执行运动反应，包括呼吸，比 我们迄今为止所想象的。

DESCRIPTION (Applicant's abstract): Previous studies from our laboratory and others have demonstrated that the cerebellum, particularly the rostral fastigial nucleus (FNR), plays a facilitatory role in the respiratory response to stress, especially to severe hypercapnia. To date, the mechanisms underlying cerebellar involvement in the respiratory response to hypercapnia remain unknown. Recent evidence utilizing both in vivo and in vitro (cell culture) techniques raises the possibility that some FNR neurons may be chemosensitive. Therefore, we hypothesize that the ability of the cerebellum to modulate the ventilatory response to acidic stimulation (CO2/H+) is, at least partially, attributed to activation of FNR chemosensitive neurons. Furthermore, we will investigate synaptic projections and neurotransmitters utilized by these chemosensitive neurons to modulate the respiratory response. Specific aims are to: 1) determine the unique involvement of the FNR neurons in the respiratory response to hypercapnia as compared to other deep cerebellar nuclei; 2) verify the presence, location and electrophysiological characteristics of chemosensitive neurons within the FNR responsible for respiratory augmentation to focal tissue acidification; 3) identify the synaptic connections of the FNR neurons essential to this FNR-mediated respiratory response; and 4) demonstrate the involvement of glutamate and/or gamma-aminobutyrate (GABA) as potential neurotransmitters in this FNR efferent pathway. This proposal will elucidate how the cerebellum facilitates the respiratory response to CO2/H+ stimulation by using multi-disciplinary approaches (electrophysiology, immunohistochemistry and pharmacology). The results will substantially broaden our general knowledge of the central network involved in chemical control of breathing and enhance our understanding of the neurochemical mechanisms underlying centrally mediated respiratory responses to physiological stress, such as exercise. Perhaps, more exciting is the emerging concept that the cerebellum may be far more involved in the planning and executing of motor responses, including respiration, than we have heretofore imagined.