BRAINSTEM NEURAL NETWORKS AND AIRWAY DEFENSIVE REFLEXES

描述：（改编自申请人摘要） 这项研究的目的是定义脑干神经网络 引起气道呼吸运动模式的机制 防御反射，即，咳嗽和呼气反射。尖峰序列 分析方法（例如，互相关、重力）将被用于 同时检测和评估多个节点之间的功能连接 记录了猫的神经元。 导出的网络模型的可扩展性 将通过计算机模拟进行测试。假想 机械刺激会诱发咳嗽和呼气反射 胸内气管和喉，分别，在去大脑， 瘫痪的，换气的猫 具体目标I：识别神经元中的 传递气道传入信息的孤束核 受体引发咳嗽，并确定其有效的连接与 靶神经元分布于延髓呼吸神经元， 确定他们在虚拟咳嗽期间的平行和顺序反应。 具体目标II：定义之间的并发功能交互 生理学表征的延髓呼吸神经元，和 确定他们在虚拟咳嗽期间的平行和顺序反应。 具体目标III：识别孤束核中的神经元， 从呼吸道感受器传递传入信息引起呼气 反射，并定义它们与目标神经元的有效连接 分布于延髓呼吸神经元网络。 具体目标 IV：定义生理学之间的并发功能相互作用 特征的延髓呼吸神经元，并确定其平行 和在虚拟呼气反射期间的顺序反应。 具体目标 V：确定止咳药（可待因， 对咳嗽受体中继神经元活性的影响， 延髓呼吸神经元及其功能连接。 呼吸道防御反射对于呼吸道疾病患者的日常生存至关重要。 患有和没有肺部疾病的人;他们也可以加剧其他 病理条件。 这些研究将提供基本信息， 这可能有助于未来开发更有效的治疗方法， 干预涉及这些反射的疾病。

DESCRIPTION: (Adapted from the applicant's abstract) The goal of the proposed research is to define brainstem neural network mechanisms that give rise to the respiratory motor patterns of airway defensive reflexes, i.e., cough and expiration reflex. Spike train analysis methods (e.g., cross-correlation, gravity) will be used to detect and evaluate functional connectivity among many simultaneously recorded neurons in cats. The plausibility of network models derived from this approach will be tested with computer simulations. Fictive cough and the expiration reflex will be evoked by mechanical stimulation of the intrathoracic trachea and larynx, respectively, in decerebrated, paralyzed, ventilated cats. Specific Aim I: Identify neurons in the nucleus tractus solitarius that relay afferent information from airway receptors eliciting cough, and define their effective connectivity with target neurons distributed in the medullary respiratory neurons, and determine their parallel and sequential responses during fictive cough. Specific Aim II: Define concurrent functional interactions among physiologically characterized medullary respiratory neurons, and determine their parallel and sequential responses during fictive cough. Specific Aim III: Identify neurons in the nucleus tractus solitarius that relay afferent information from airway receptors eliciting the expiration reflex, and define their effective connectivity with target neurons distributed in the medullary respiratory neuronal network. Specific Aim IV: Define concurrent functional interactions among physiologically characterized medullary respiratory neurons, and determine their parallel and sequential responses during fictive expiration reflex. Specific Aim V: Determine the effects of antitussive agents (codeine, dextromethorphan) on the activity of cough receptor relay neurons, medullary respiratory neurons, and their functional connectivity. Airway defensive reflexes are essential for the day-to-day survival of individuals with and without lung disease; they can also exacerbate other pathological conditions. These studies will contribute basic information that could be useful for future development of more effective therapeutic interventions for disorders involving these reflexes.