Mechanisms and sites of ventilatory neurogenesis

描述（由申请人提供）：在脑干的脑桥和延髓部分内产生“自动”呼吸运动，无需有意识的努力。Eupnea是正常的呼吸。在正常呼吸中，足够的氧气被供应到身体，二氧化碳被去除以满足代谢需求。如果正常呼吸停止，就会出现缺氧。严重的缺氧会引起喘息，这是一种“自动复苏”机制。“我们提出，从根本上不同的机制产生eupnea和喘息。正常呼吸反映了脑桥延髓神经元回路的输出，而喘息是由延髓起搏器的放电产生的。在正常呼吸期间，这些起搏机制被抑制。研究将评估有关呼吸节律产生的神经生理机制的多种假设。其中包括一项评估，即具有与产生喘息一致的放电特征的髓神经元在突触传递被阻断后将继续节律性爆发。因此，这些脉冲串被认为代表“起搏器放电”。“这些研究需要从正常呼吸到喘息的可逆变化。将连续获得神经元活动的细胞外和细胞内记录。将应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这些研究。缺氧诱导的喘息可以被可逆地诱导，在给予药理学试剂以阻断突触传递后维持活力，并且脑干的最小运动使得神经元活动的细胞外和细胞内记录成为可能。这些研究的结果将提供重要的和独特的信息，以产生正常呼吸的机制。这些信息可能会提供对人类通气控制功能障碍的深入了解，如“睡眠呼吸暂停”或“婴儿猝死综合征”。"

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."