CELLULAR ELECTROPHYSIOLOGY OF THE SUPRACHIASMATIC NUCLEI

描述：哺乳动物的昼夜节律是由分子钟产生的 位于视交叉上核（SCN）的单个神经元内。 的 分子钟驱动SCN神经元的活动， 在白天比在晚上更高的频率电位。 的 这种活动的潜在机制尚不清楚，但必须涉及昼夜节律 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 和相移昼夜节律也调节离子通道的活性 这是SCN神经元有节奏放电所必需的。 在SCN 这些问题由于神经元表型的异质性而变得复杂 以及在不同时间的信号转导偶联的差异。 昼夜节律日 电生理学和形态学技术将是 用于研究SCN神经元中的神经递质信号转导。 该提案的具体目标是：1）审查机制 将神经递质受体与离子通道偶联， SCN神经元的动作电位产生。 2)确定的作用 神经递质受体与离子偶联的昼夜节律时间 渠道 3)研究褪黑激素受体如何调节 SCN中的其他神经递质受体。 4)将形态学分类 对特定神经递质有反应的细胞类型。 鉴定 SCN中独特的离子电导和信号转导途径将 为睡眠和昼夜节律紊乱的临床治疗提供新的靶点。

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.