DEVELOPMENTAL CONTROL OF THE DIAPHRAGM AND UPPER AIRWAYS

描述(改编自申请人的摘要)：本提案将 颧舌骨和膈骨的出生后发育特征 运动神经元，通过将膜上的生理变化联系起来 随着解剖学的变化，电导和尖峰特性。优势所在 呼吸肌收缩的程度由呼吸肌收缩的数量决定 呼吸运动神经元的激活及其放电率。这两个 神经元被激活的顺序及其放电率是 它们的静息电导的函数，即膜的数量 频道在任何给定的时间开放。大多数膜通道是受控制的 由神经递质和/或由人的内在电状态 细胞膜。这两个过程的平衡变化最大的是 在出生后的发育过程中戏剧性的。申请人对以下项目感兴趣 这些过程发生在两个呼吸运动神经元中， 影响横隔肌和颧舌肌的功能。激活 这两块肌肉必须协调起来，才能将空气输送到肺部 最小的努力；这可能与 婴儿猝死综合征的病理生理学研究在过去 在此期间，申请人证明甘氨酸对 由于静息膜电导在3周时增加， 这些与年龄相关的静息电导的增加是由于 开放的钾通道数量的增加。建议数 将在#年对膝舌肌和膈运动神经元进行研究。 大鼠脑干和脊髓的切片制备。视觉上 将对四个不同年龄段的运动神经元进行研究 (1-2、5-7、13-15和19-22天)与膜片钳结合 记录，三维神经元重建和 某些受体和离子通道的免疫细胞化学定位。 该应用将：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四个阶段 出生后发育；2)确定特定的钾通道， 有助于膜电导和尖峰电流的增加 特征；3)探索细胞内途径介导的 钾电导增强。

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.