suprachiasmatic nucleus (SCN) networks and efferent signals

描述（由申请人提供）：自从视交叉上核（SON）首次被发现为大脑时钟以来的几十年中，其功能、细胞元件和网络组织已经为通过分析细胞、组织和生物体在行为、生理和分子水平上理解大脑功能设定了标准。最初认为SCN是由均匀的振荡器组成的，向身体发出相干信号。现在很清楚，大脑时钟是由功能上不同的“昼夜节律钟细胞”组成的，这些细胞可以组织成不同的振荡网络。此外，在许多器官中存在振荡器和振荡组织。仓鼠是选择的主题，因为它具有非常精确的每日节律、显著的光周期反应和大量的背景研究，这些研究表明a）在不同的SCN细胞中的时钟基因和蛋白质表达揭示了“非振荡“门”细胞以及振荡细胞的存在（基于时钟基因表达和电节律性），B）基于某些SCN内细胞是依赖于眼睛的“从属振荡器”的证据，以及c）SCN子区域的神经元到每个已知脑靶位点的传入和传出连接。拟议的研究将描述SCN活动，以评估中枢和外周振荡器响应的网络可塑性的后果。第一个目标集中在SCN，表征网络可塑性。实验需要在各种实验光条件下，使用昼夜节律时相（时钟基因）和神经激活（FOS）的分子标记物检查SCN的振荡和非振荡细胞的时相（目的1）。下一个重点是节律性SCN外部位，检查脑和外周靶组织中诱导的节律性（目的2和3）。(Aim 4）建议使用数学建模来提供可检验的假设，并将生理学研究的结果概念化。我们的假设是，我们将能够描绘特定的SCN内网络的活动和大脑靶点之间的关系，从而解决长期寻求的SCN异质性的解释。

DESCRIPTION (provided by applicant): In the decades since the suprachiasmatic nucleus (SON) was first discovered as the brain clock, its function, cellular elements, and network organization have set the standard for understanding brain function at behavioral, physiological and molecular levels through analysis of cells, tissue and organisms. It was initially thought that the SCN was constituted of a uniform population of oscillators, sending out a coherent signal to the body. It is now clear that the brain clock is constituted of a functionally heterogeneous "circadian clock cells" that can be organized into distinct oscillating networks. Furthermore, there are oscillators and oscillating tissues in numerous organs. The hamster is the subject of choice as it has very precise daily rhythms, significant photoperiodic responses and a wealth of background studies indicating a) clock gene and protein expression in distinct SCN cells reveal the presence of "non-oscillating "gate" cells as well as oscillator cells (based on clock gene expression and electrical rhythmicity), b) on evidence that some intra-SCN cells are "slave oscillators" dependent on the eye, and c) on afferent and efferent connections of neurons of SCN sub-regions to each known brain target sites. The proposed research will characterize SCN activity to assess the consequence of network plasticity on central and peripheral oscillator responses. The first aim focuses on the SCN, characterizing network plasticity. The experiments entail examination of the phase of oscillating and non-oscillating cells of the SCN, under various experimental photic conditions, using molecular markers of circadian phase (clock genes) and neural activation (FOS) (Aim 1). The next focus is on rhythmic extra-SCN sites, examining rhythmicity induced in brain and peripheral target tissues (Aims 2 and 3). (Aim 4) proposes to use mathematical modeling to provide testable hypotheses and to conceptualize the results of the physiological studies. The hypothesis is that we will be able to delineate the relationship between activity of specific intra-SCN networks and brain target sites thereby addressing the long-sought explanation for SCN heterogeneity.