CEREBELLUM--ROLE IN THE CHEMICAL CONTROL OF BREATHING

描述(申请人摘要)：我们实验室以前的研究和 其他人已经证明了小脑，特别是吻部 顶核(FNR)在呼吸反应中起促进作用 加重压力，尤指严重的高碳酸血症。到目前为止，潜在的机制 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 技术提高了一些FNR神经元可能对化疗敏感的可能性。 因此，我们假设小脑调节大脑活动的能力 对酸刺激(CO2/H+)的通风反应至少部分是， 归因于FNR化疗敏感神经元的激活。此外，我们还将 研究这些基因所利用的突触投射和神经递质 调节呼吸反应的化学敏感神经元。具体目标是 目的：1)确定FNR神经元在呼吸中的独特参与 与其他小脑深部核团相比，对高碳酸血症的反应；2)验证 脉搏波的存在、定位及电生理特征 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的突触联系 对这种FNR介导的呼吸反应至关重要的神经元；以及4)证明 谷氨酸和/或γ-氨基丁酸(GABA)作为潜在的参与 此FNR传出通路中的神经递质。这项提议将澄清 小脑如何促进对CO2/H+刺激的呼吸反应 使用多学科方法(电生理学、免疫组织化学 和药理学)。结果将极大地拓宽我们的常识 参与呼吸和增强化学控制的中枢网络 我们对中枢调节的神经化学机制的理解 对生理压力的呼吸反应，如运动。也许，更多 令人兴奋的是一个新兴的概念，即小脑可能更多地参与其中 在包括呼吸在内的运动反应的计划和执行中， 到目前为止，我们一直在想象。

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.