DEVELOPMENTAL CONTROL OF THE DIAPHRAGM AND UPPER AIRWAYS

描述（改编自申请人的摘要）：本提案将 描述颏舌肌和膈肌的出生后发育 运动神经元，通过相关的生理变化，在膜 电导和尖峰特性与解剖结构的变化。强度 呼吸肌收缩的速度取决于 呼吸运动神经元激活及其放电速率。两者 神经元被激活的顺序和它们的放电速率是 这是它们的静息电导的函数，也就是说， 渠道随时开放。大多数膜通道都是受控的 通过神经递质和/或通过神经元的固有电状态， 细胞膜这两个过程的平衡变化最大 在产后发育过程中的戏剧性。申请人感兴趣的是 这些过程发生在两个呼吸运动神经元中， 影响膈肌和颏舌肌的功能。激活 这两块肌肉必须协调一致，才能将空气送入肺部， 最小的努力;这可能特别相关的 婴儿猝死综合征（SIDS）的病理生理学。过去 在此期间，申请人确定甘氨酸显著贡献 到3周时静息膜电导的增加， 这些与年龄相关的静息电导增加是由 开放钾通道数量的增加。拟议 研究将在颏舌和膈运动神经元进行， 大鼠脑干和脊髓的切片制备。视觉上 将对四个不同年龄组的运动神经元进行研究 (1-2 5-7、13-15和19-22天）联合膜片钳技术 记录，三维神经元重建， 某些受体和离子通道的免疫细胞化学定位。 该应用程序将：1）检查甘氨酸的解剖学和生理学， GABA和谷氨酸神经递质系统在这四个阶段， 出生后发育; 2）识别特定的钾通道， 有助于增加膜电导和尖峰 特征;和3）探索介导细胞内途径， 增强钾电导。

DESCRIPTION (Adapted from the applicant's abstract): This proposal will characterize the postnatal development of the genioglossal and phrenic motoneurons, by correlating physiological changes in membrane conductance and spiking properties with changes in anatomy. The strength of respiratory muscle contraction is determined by the number of respiratory motoneurons activated and their rate of discharge. Both the order in which the neurons are activated and their discharge rates are a function of their resting conductance, that is, the number of membrane channels open at any given time. Most membrane channels are controlled by neurotransmitters and/or by the intrinsic electrical state of the cell membrane. The change in the balance of these two processes are most dramatic during postnatal development. The applicant is interested in these processes that occur in the two respiratory motoneurons that affect the performance of the diaphragm and genioglossus. Activation of these two muscles must be coordinated to move air into the lungs with the least effort; this may be particularly relevant to the pathophysiology of Sudden Infant Death Syndrome (SIDS). In the past period, the applicant established that glycine significantly contributed to the increase in resting membrane conductance that occurs at 3 weeks, and that these age-related increases in resting conductance result from an increase in the number of open potassium channels. The proposed studies will be performed on genioglossal and phrenic motoneurons in slice preparations of the rat brainstem and spinal cord. Visually identified motoneurons will be studied from four different age groups (1-2, 5-7, 13-15 and 19-22 days) with a combination of patch-clamp recording, three-dimensional neuronal reconstruction and immunocytochemical localization of certain receptors and ion channels. The application will: 1) examine the anatomy and physiology of glycine, GABA, and glutamate neurotransmitter systems at the four stages during postnatal development; 2) identify specific potassium channels that contribute to the increase in membrane conductance and spike characteristics; and 3) explore the intracellular pathways mediating the enhanced potassium conductance.