CEREBELLUM--ROLE IN THE CHEMICAL CONTROL OF BREATHING

小脑——化学控制呼吸的作用

• 批准号: 2903257
• 负责人: DONALD T FRAZIER
• 金额: $ 24.42万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2903257
• 关键词: Mammalia; acidity /alkalinity; brain mapping; cerebellum; chemoreceptors; electrophysiology; gamma aminobutyrate; glutamates; hypercapnia; immunocytochemistry; neurochemistry; neuroregulation; neurotransmitter transport; pulmonary respiration; respiration regulatory center

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.

描述（申请人的摘要）：我们实验室的先前研究和 其他人证明了小脑，尤其是the 快速核（FNR）在呼吸反应中起促进作用 压力，尤其是严重的高碳酸盐。迄今为止，机制 小脑参与呼吸道对高碳酸血症的反应仍然存在 未知。使用体内和体外（细胞培养）的最新证据 技术提高了某些FNR神经元可能具有化学敏感性的可能性。 因此，我们假设小脑调节小脑的能力 对酸性刺激（CO2/H+）的通气反应至少部分是 归因于FNR化学敏感神经元的激活。此外，我们会的 研究这些使用的突触投影和神经递质 化学敏感性神经元调节呼吸反应。具体目标是 至：1）确定FNR神经元在呼吸道中的独特参与 与其他深小脑核相比，对高碳酸疾病的反应； 2）验证 的存在，位置和电生理特征 FNR内的化学敏感性神经元负责呼吸增强 进行局灶性组织酸化； 3）确定FNR的突触连接 FNR介导的呼吸反应必不可少的神经元； 4）演示 谷氨酸和/或γ-氨基丁酸（GABA）的参与为潜力 该FNR传出途径中的神经递质。该建议将阐明 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 和药理学）。结果将大大扩大我们的一般知识 涉及呼吸和增强化学控制的中央网络 我们对集中介导的神经化学机制的理解 对生理压力的呼吸反应，例如运动。也许更多 令人兴奋的是新兴的概念，即小脑可能更多地参与 在计划和执行电动机响应（包括呼吸）中， 我们迄今想象的。