CONTROL OF BREATHING DURING PHYSIOLOGIC CONDITIONS

延髓腹外侧区(VLm)和横隔膜传入神经的作用 (Da)在麻醉下控制呼吸仍然存在争议， 而它们在非麻醉状态下的作用更具推测性。 因此，我们的目标是测试关于VLM的有争议的假设 生理条件下的DA。对于VLM，我们将学习清醒， 麻醉和熟睡的山羊使用：1)长期植入的热模式 降温(20度)，从而造成可逆性神经元功能障碍 在VLM表面附近的部位，以及2)微量注射红藻氨酸以 在离散的VLM部位造成永久性神经元功能障碍。使用 降温、功能障碍的影响不会被代偿性变化所掩盖 这可能发生在永久性损伤之前和之后的研究之间。使用 永久性损伤核团的潜在功能可以被识别。 关键假设是：1)双侧功能障碍的区域包括 后梯形核(RTN区)会引起呼吸暂停或 呼吸困难；在几种呼吸亢进的情况下 不会导致呼吸暂停，但会统一减弱呼吸；2) 双侧功能障碍更多地出现在中间VLM(IVLM)将 引起呼吸和呼吸肌的普遍减弱 活性，但在CO2-H+升高时衰减会更大 刺激比运动、低氧、NaCN输注和 呼吸机负荷；3)两个RTN同时功能障碍 去颈动脉化学感受器后的面积和IVLM将消失 麻醉和NREM中CO2-H+高呼吸及引起延长呼吸暂停 睡吧。检验这些假设将表明：1)RTN是否 对呼吸节律的产生以及它是否有助于 更多的背侧延髓呼吸神经元，2)IVLM整合或 处理颅内化学感受器和外周反射，3)在 这些VLM位置对CO2-H+通风敏感性至关重要， 4)在麻醉和NREM睡眠中，呼吸严重依赖于 CO2-H+刺激区、功能性RTN区和IVLM区。与DA相关的 目标，我们将研究清醒的小马。我们假设横隔膜 去传入将：1)减少增加的刺激 横隔膜，出现在正常的小马上，称为反射 作业长度补偿和通风负荷补偿；2) 在去肺神经的小马身上消除这种增加的刺激。这些 研究结果将支持DA有助于这些反射的概念。 我们的研究将为呼吸控制提供独特的见解 在生理状况和疾病期间，如婴儿猝死 综合征、Ondine‘s诅咒、睡眠呼吸暂停和慢性阻塞性肺病。

The role of the ventrolateral medulla (VLM) and diaphragmatic afferents (DA) in the control of breathing under anesthesia remains controversial, and their role in unanesthetized conditions is even more speculative. Thus our objective is to test controversial hypotheses regarding the VLM and DA during physiologic conditions. For the VLM, we will study awake, anesthetized, and asleep goats using: 1) chronically implanted thermodes to cool (20 degrees) and thereby create reversible neuronal dysfunction at sites near the VLM surface, and 2) microinjections of kainic acid to create permanent neuronal dysfunction at discrete VLM sites. With cooling, dysfunction effects are not obscured by compensatory changes that may occur between studies before and after permanent lesions. With permanent lesions the nuclei underlying functions can be identified. Key hypotheses are: 1) Bilateral dysfunction of an area that includes the retrotrapezoid nucleus (RTN area) will cause apnea or hypoventilation during eucapnia; during several hyperpneic conditions it will not cause apnea but will uniformly attenuate breathing; 2) Bilateral dysfunction more caudally in the intermediate VLM (IVLM) will cause a general attenuation of breathing and respiratory muscle activity, but the attenuation will be greater during elevated CO2-H+ stimulation than during exercise, hypoxia, NaCN infusion, and ventilatory loading; and 3) Simultaneous dysfunction of both the RTN area and the IVLM after carotid chemoreceptor denervation will eliminate the CO2-H+ hyperpnea and cause prolonged apnea in anesthesia and NREM sleep. Testing these hypotheses will suggest whether: 1) the RTN is critical for generation of respiratory rhythm and whether it facilitates more dorsal medullary respiratory neurons, 2) the IVLM integrates or processes intracranial chemoreception and peripheral reflexes, 3) in all states, these VLM sites are critical for CO2-H+ ventilatory sensitivity, and 4) in anesthesia and NREM sleep breathing is critically dependent on the CO2-H+ stimulus and functional RTN and IVLM areas. For DA related objectives, we will study awake ponies. We hypothesize diaphragmatic deafferentation will: 1) reduce the increased stimulation of the diaphragm which occurs in a normal pony as that of reflexes known as operational length compensation and ventilatory load compensation; 2) eliminate this increased stimulation in a lung denervated pony. These findings will support the concept that DA contribute to these reflexes. Our studies will provide unique insights into the control of breathing during physiologic conditions and diseases such as Sudden Infant Death Syndrome, Ondine's Curse, sleep apnea, and COPD.