Mechanisms and sites of ventilatory neurogenesis

描述（由申请人提供）：“自动”呼吸运动，不需要有意识的努力，在脑干的桥状和髓状部分产生。吐气是正常的呼吸。在eupnea中，为身体提供足够的氧气，并清除二氧化碳以满足代谢需求。如果呼吸停止，就会出现缺氧。严重的缺氧会引起喘息，这是一种“自我复苏”机制。我们提出了产生呼吸和喘息的根本不同的机制。吐气反映了脑桥延髓神经元回路的输出，而喘气则是由延髓起搏器的放电产生的。在呼吸暂停期间，这些起搏器机制被抑制。研究将评估有关产生呼吸节律的神经生理机制的多种假设。包括评估髓质神经元，其放电特征与产生喘息一致，将在突触传递受阻后继续有节奏的爆发。因此，这些爆发被认为是“起搏器放电”。研究需要从呼吸暂停到喘气的可逆变化。神经元活动的细胞外和细胞内记录将连续获得。将使用药物阻断突触传递。“新生”和“幼年”大鼠的原位制备特别适合于这些研究。缺氧诱导的喘息可以被可逆地诱导，通过药物阻断突触传递可以维持生存能力，脑干的最小运动使神经元活动的细胞外和细胞内记录成为可能。这些研究的结果将为正常呼吸产生的机制提供重要而独特的信息。这些信息可能会对人类控制通气的功能障碍，如“睡眠呼吸暂停”或“婴儿猝死综合症”提供深入的了解。

DESCRIPTION (provided by applicant): "Automatic" breathing movements, which occur without conscious effort, are generated within the pontile and medullary portions of the brainstem. Eupnea is normal breathing. In eupnea, sufficient oxygen is supplied to the body and carbon dioxide is removed to meet the metabolic demands. If eupnea ceases, hypoxia will develop. Severe hypoxia recruits gasping, which is a mechanism for "autoresuscitation." We have proposed that fundamentally different mechanisms generate eupnea and gasping. Eupnea reflects the output of a pontomedullary neuronal circuit whereas gasping is generated by the discharge of medullary pacemakers. During eupnea, these pacemaker mechanisms are suppressed. Studies will evaluate multiple hypotheses concerning the neurophysiological mechanisms by which respiratory rhythms are generated. Included will be an evaluation that medullary neurons, with discharge characteristics consonant with generating the gasp, will continue rhythmic bursts following a blockade of synaptic transmission. Hence, these bursts are considered to represent a "pacemaker discharge." The studies require the reversible alteration from eupnea to gasping. Both extracellular and intracellular recordings of neuronal activities will be obtained continuously. Agents will be applied to block synaptic transmission. The in situ preparations of the "neonatal" and "juvenile" rats are uniquely suited for these studies. Hypoxia-induced gasping can be reversibly induced, viability is maintained following administration of pharmacological agents to block synaptic transmission, and the minimal movements of the brainstem make possible the extracellular and intracellular recordings of neuronal activities. Results of these studies will provide significant and unique information as to the mechanisms by which normal breathing is generated. Such information might provide insights into dysfunctions of the control of ventilation in humans, such as in "sleep apnea" or the "sudden infant death syndrome."