Mechanisms of Fast Oscillations in Motor Discharges

电机放电中快速振荡的机制

• 批准号: 7425347
• 负责人: IRENE C SOLOMON
• 金额: $ 27.09万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7425347
• 关键词: Algorithms; Area; Biochemical; Biological Assay; Brain Stem; Cell Nucleus; Chemoreceptors; Condition; Connexins; Coupling; Dorsal; Fourier Transform; Frequencies; Gap Junctions; Generations; Hypoglossal nerve structure; Immunoblotting; In Situ; In Vitro; Label; Mediating; Motor; Mus; Muscle; Nerve; Neuraxis; Neurons; Parvalbumins; Peripheral; Physiological; Play; Preparation; Protein Isoforms; Protocols documentation; Research Proposals; Respiratory Diaphragm; Role; Structure of phrenic nerve; Synapses; Synaptic Transmission; System; Time; Tissue Sample; Tissues; Uncoupling Agents; Work; connexin 36; gamma-Aminobutyric Acid; genetic manipulation; in vivo; indexing; inhibitory neuron; motor control; neuroregulation; receptor; research study; respiratory; synaptic inhibition; time use

DESCRIPTION (provided by applicant): Fast oscillatory neuronal activity is a prominent feature observed in many areas of the central nervous system (CNS), including CNS regions associated with respiratory motor control. In the respiratory neural control system, it has long been recognized that fast oscillatory rhythms are present in inspiratory-related muscles, nerves, and neurons, and that these fast rhythmic oscillations provide an index of short-time scale synchronization within the inspiratory burst. The neuronal mechanisms that underlie fast oscillations in the CNS are poorly understood. It has been hypothesized, however, that interneuronal gap junctions and fast inhibitory synaptic mechanisms play a critical role in the generation of fast network oscillations. Recent observations further indicate that gap junctions, composed of the neuron specific gap junction protein connexin36 (Cx36), among GABAergic inhibitory neurons may participate in the generation of fast oscillations in some areas of the CNS. The experiments proposed in this application will use biochemical and immunohistochemical analyses in conjunction with in vivo and in vitro experiments in wild type and Cx36- deficient mice to further define the roles of brainstem gap junctions (including gap junctions composed of Cx36) and GABAA-mediated synaptic inhibition in the generation of fast oscillations in the inspiratory neural control system. The specific aims of this research proposal are: (1) investigate the effects of genetic manipulation (deletion) of the neuronal gap junction protein Cx36 on fast oscillatory rhythms in inspiratory motor discharges, (2) investigate the effects of pharmacological blockade of GABAA receptors on fast oscillatory rhythms in inspiratory motor discharges in Cx36-deficient mice, (3) investigate the effects of pharmacological blockade of gap junctions and GABAA receptors in the dorsal respiratory group (DRG), rostral ventral respiratory group (rVRG), and phrenic motor nucleus (PMN) on fast oscillatory rhythms in inspiratory discharges, (4) identify the repertoire of gap junction proteins in GABAergic neurons in respiratory-related medullary regions, and (5) investigate whether the expression levels of other neuronal gap junction proteins in respiratory-related brainstem regions are altered in Cx36-deficient mice.

描述（由申请人提供）：快速振荡神经元活动是在中枢神经系统（CNS）的许多区域观察到的突出特征，包括与呼吸运动控制相关的CNS区域。在呼吸神经控制系统中，长期以来一直认识到，在吸气相关的肌肉，神经和神经元中存在快速的振荡节奏，并且这些快速的节奏振荡在灵感爆发中提供了短期比例同步指数。中枢神经系统中快速振荡的神经元机制知之甚少。然而，已经假设，神经元间隙连接和快速抑制性突触机制在快速网络振荡的产生中起着至关重要的作用。最近的观察结果进一步表明，在GABA能抑制性神经元中，由神经元特异性间隙连接蛋白连接（CX36）组成的间隙连接可能参与某些CNS的某些区域的快速振荡。 The experiments proposed in this application will use biochemical and immunohistochemical analyses in conjunction with in vivo and in vitro experiments in wild type and Cx36- deficient mice to further define the roles of brainstem gap junctions (including gap junctions composed of Cx36) and GABAA-mediated synaptic inhibition in the generation of fast oscillations in the inspiratory neural control 系统。这项研究建议的具体目的是：（1）研究神经元间隙连接蛋白CX36对启发性运动放电中快速振荡性节律的遗传操纵（缺失）的影响，（2）研究GABAA受体对快速振动性Rhythms insectal Rhythm的药理阻滞的影响CX666-DECRICTICT in cosient in Presistient in Pristient of Inspiration in cx36-defient（3）。在灵感放电中快速振荡性节奏上，背侧呼吸系统（DRG），腹侧腹侧呼吸核（RVRG）和Phrenic运动核（PMN）对间隙连接和GABAA受体的阻塞阻塞（4）在CX36缺陷型小鼠中，其他神经元间隙连接蛋白的表达水平改变了。