CNS SEROTONERGIC NEURONS AND BREATHING

关于中枢神经系统的最新知识 控制呼吸的神经通路和神经递质 不完整。我们一直在使用神经解剖学和 神经药理学技术，以扩展我们的 在这一领域的知识，并发现刺激尾部 中缝核团引起呼吸运动流出的改变 膈神经和喉返神经是由 5-羟色胺能神经通路。这样做的总体目标是 建议研究5-羟色胺能神经元在脑内的作用 猫呼吸控制中的中缝尾侧核团。这个 具体目标是：1)识别尾部的联系 中缝核团与其他已建立的呼吸核团，包括 背侧呼吸组、腹侧呼吸组、Botzinger 复合体、脑桥呼吸群和喉返神经 疑核的运动神经元；2)确定5-羟色胺是否 一种神经递质，由尾部中缝投射到这些 呼吸核团；3)确定5-羟色胺是否神经支配 在这些呼吸系统中功能鉴定的呼吸神经元 核团；4)确定5-羟色胺参与 介导膈神经和喉返神经的变化 刺激中缝尾侧核所引起的神经活动。 使用的方法包括：凝集素顺行示踪， 荧光染料逆行追踪，免疫组织化学， 膈神经记录，喉返神经记录， 电和化学(L-谷氨酸)刺激大脑核团， 呼吸神经元活动的细胞外记录，以及 加压微量注射影响5-羟色胺能活动的药物。 迫切需要进一步的基础研究来界定 中枢神经系统的突触关系与神经递质 呼吸神经元。本研究也具有重要的临床意义。 随着对呼吸系统神经化学基础知识的增加 控制将增加改善的可能性 呼吸系统疾病的药物干预包括 睡眠呼吸暂停、婴儿猝死综合征与慢性阻塞性肺疾病 肺部疾病。

Current knowledge concerning the central nervous system neuropathways and neurotransmitters controlling respiration is incomplete. We have been using neuroanatomical and neuropharmacological techniques in order to extend our knowledge in this area and found that stimulation of the caudal raphe nuclei produces changes in respiratory motor outflow of the phrenic and recurrent laryngeal nerves that are mediated by serotonergic neuropathways. The overall objective of this proposal is to investigate the role of the serotonergic neurons of the caudal raphe nuclei in respiratory control in the cat. The specific aims are to: 1) Identify the connections of the caudal raphe nuclei with other established respiratory nuclei including the dorsal respiratory group, ventral respiratory group, Botzinger Complex, pontine respiratory group and recurrent laryngeal nerve motoneurons of the nucleus ambiguus; 2) Determine if serotonin is a neurotransmitter used by caudal raphe projections to these respiratory nuclei; 3) Determine if serotonin innervates functionally identified respiratory neurons in these respiratory nuclei; and 4) Determine the involvement of serotonin in mediating the changes in phrenic nerve and recurrent laryngeal nerve activity evoked by stimulation of the caudal raphe nuclei. Methods to be used include: anterograde tracing with lectin, retrograde tracing with fluorescent dyes, immunohistochemistry, phrenic nerve recording, recurrent laryngeal nerve recording, electrical and chemical (L-glutamate) stimulation of brain nuclei, extracellular recording of respiratory neuron activity, and pressure microinjection of drugs affecting serotonergic activity. There is a critical need for further basic research to define the synaptic relationships and neurotransmitters of central respiratory neurons. This research is of clinical importance also as increased knowledge of the neurochemical basis of respiratory control will increase the possibilities of improving pharmacological intervention in respiratory disorders including sleep apnea, sudden infant syndrome and the chronic obstructive pulmonary diseases.