CELLULAR ELECTROPHYSIOLOGY OF THE SUPRACHIASMATIC NUCLEI

描述：哺乳动物的昼夜节律是由分子时钟产生的 位于视交叉上核(SCN)的单个神经元内。这个 分子时钟驱动SCN神经元的活动，激发活动 白天的电位频率高于夜间。这个 这种活动背后的机制尚不清楚，但肯定与昼夜节律有关。 参与动作电位产生的离子通道的调节。 我们的假设是改变SCN神经元活动的神经递质 相移昼夜节律也调节离子通道的活动。 它们是SCN神经元有节奏地放电所必需的。在SCN中 这些问题因神经元表型的异质性而变得复杂。 以及不同时间的信号转导耦合的差异。 昼夜节律日。电生理和形态技术将是 用于研究SCN神经元中的神经递质信号转导。 该提案的具体目的是：1)审查机制 将神经递质受体偶联到离子通道，这对 SCN神经元的动作电位产生。2)确定 神经递质受体与离子偶联的昼夜时间 频道。3)研究褪黑素受体是如何调节 脊髓核内的其他神经递质受体。4)对形态进行编目 对特定神经递质作出反应的细胞类型。身份识别 SCN中独特的离子电导和信号转导途径 为临床治疗睡眠和昼夜节律紊乱提供新的靶点。

DESCRIPTION: Mammalian circadian rhythms are generated by a molecular clock located within individual neurons of the suprachiasmatic nucleus (SCN). The molecular clock drives the activity of SCN neurons which fire action potentials at a higher frequency during the day than during the night. The mechanisms underlying this activity are unknown, but must involve circadian regulation of ion channels involved in the generation of action potentials. Our hypothesis is that neurotransmitters which alter SCN neuronal activity and phase shift circadian rhythms also modulate the activity of ion channels which are necessary for the rhythmic firing of SCN neurons. In the SCN these questions are complicated by the heterogeneity of neuronal phenotypes and differences in signal transduction coupling at different times of the circadian day. Electrophysiological and morphological techniques will be used to investigate neurotransmitter signal transduction in SCN neurons. The specific aims of the proposal are to: 1) Examine the mechanisms coupling neurotransmitter receptors to ion channels which are important for action potential generation in SCN neurons. 2) Determine the role of circadian time in the coupling of neurotransmitter receptors to ion channels. 3) Investigate how melatonin receptors modulate the activity of other neurotransmitter receptors in the SCN. 4) Catalogue the morphological cell types which respond to specific neurotransmitters. Identification of unique ion conductances and signal transduction pathways in the SCN will provide new targets for clinical treatment of sleep and circadian disorders.