SEROTONIN AT THE PHRENIC MOTOR NECLEUS AND RESPIRATION

我们已经表明，5-羟色胺是目前在膈运动核（PMN） 似乎起源于脑干中缝核的神经元。 的 本研究提案的总体目标是通过以下方式确认 神经化学技术，中缝核是主要来源， 5-羟色胺在中性粒细胞，并评估生理技术， 这种神经递质的功能是在脊髓呼吸系统 原子核 其具体目的是：1）证实中缝核是 PMN中5-羟色胺的主要来源以及 这些核团中的每一个都有贡献; 2）确定 中性粒细胞的肾上腺素能活动的改变对正常的 呼吸活动; 3）确定哪些变化， 活动在中性粒细胞做的呼吸反应引起的 高碳酸血症和缺氧的生理刺激和4）确定什么 中性粒细胞的肾上腺素能活动的改变， 中缝核和已知的脑干呼吸核。 所用方法 包括：1）化学损毁中缝核和测量 5-羟色胺在中性粒细胞的高压液相色谱法; 2）测量 呼吸活动的几个指数（潮气量，呼吸率， 分钟通气量、气管压、潮气末CO2和血气） 麻醉和去脑猫，配有呼吸速度描记器; 3） 鞘内注射药物以改变脑组织中的血清素活性 中性粒细胞和4）电和化学（谷氨酸微量注射）刺激 脑干细胞核的结构 这些研究很重要，因为它们将提供 关于控制PMN的神经通路和神经递质的信息 活动 这些信息对于理解正常呼吸很重要 但对于了解中枢神经系统呼吸系统疾病至关重要。 可能 涉及PMN及其中枢输入的呼吸系统疾病包括 婴儿猝死综合征和睡眠呼吸暂停。 对联合国作用的认识 参与中枢控制的神经递质和神经通路 呼吸将进一步加深我们对这些呼吸系统疾病的理解， 并可能为这些疾病的治疗提供合理的依据。

We have shown that serotonin is present at the phrenic motor nucleus (PMN) in neurons that appear to originate from the brainstem raphe nuclei. The overall objectives of this research proposal are to confirm by neurochemical techniques that the raphe nuclei are the primary source of serotonin at the PMN and to evaluate by physiological techniques what the function of this neurotransmitter is at this spinal cord respiratory nucleus. The specific aims are to: 1) confirm that the raphe nuclei are the primary source(s) of the serotonin at the PMN and how much of the serotonergic innervation each of these nuclei contributes; 2) determine what alterations in serotonergic activity at the PMN do to normal respiratory activity; 3) determine what alterations in serotonergic activity at the PMN do to the respiratory responses elicited by the physiological stimuli of hypercapnia and hypoxia and 4) determine what alterations in serotonergic activity at the PMN do to stimulation of the raphe nuclei and known brainstem respiratory nuclei. Methods to be used include: 1) chemical lesioning of the raphe nuclei and measurement of serotonin at the PMN by high pressure liquid chromatography; 2) measurement of several indices of respiratory activity (tidal volume, respiratory rate, minute volume, trachael pressure, end tidal CO2 and blood gases) in anesthetized and decerebrated cats fitted with a pneumotachograph; 3) intrathecal administration of drugs to alter serotonergic activity at the PMN and 4) electrical and chemical (glutamate microinjection) stimulation of brain stem nuclei. These studies are important since they will provide information about the neuropathways and neurotransmitters controlling PMN activity. This information is important for understanding normal breathing but is critical for understanding CNS respiratory disorders. Possible respiratory disorders involving the PMN and its central inputs include Sudden Infant Death Syndrome and Sleep Apnea. Knowledge of the role of the neurotransmitters and neuropathways involved in the central control of respiration will further our understanding of these respiratory disorders, and may provide a rational basis for the treatment of these disorders.