suprachiasmatic nucleus (SCN) networks and efferent signals

描述（由申请人提供）：自视交叉上核（SON）首次被发现为大脑时钟以来的几十年里，它的功能、细胞成分和网络组织已经通过对细胞、组织和生物体的分析，在行为、生理和分子水平上为理解大脑功能设定了标准。最初认为SCN是由一群均匀的振荡器组成的，它们向身体发出连贯的信号。现在很清楚，大脑时钟是由功能不同的“生物钟细胞”组成的，这些细胞可以被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。仓鼠之所以成为研究对象，是因为它具有非常精确的日常节律、显著的光周期反应和大量的背景研究表明：a)时钟基因和蛋白质在不同的SCN细胞中的表达揭示了“非振荡”门细胞和振荡细胞的存在（基于时钟基因表达和电节律性）；b)有证据表明，一些SCN内细胞是依赖于眼睛的“从振荡器”。c) SCN亚区神经元与每个已知脑靶点的传入和传出连接。拟议的研究将表征SCN活动，以评估网络可塑性对中心和外围振荡器响应的影响。第一个目标侧重于SCN，表征网络的可塑性。实验需要在不同的实验光条件下，使用昼夜节律阶段（时钟基因）和神经激活（FOS）的分子标记来检查SCN的振荡和非振荡细胞的阶段（Aim 1）。下一个重点是有节奏的scn外部位，检查大脑和外周靶组织诱导的节律性（目标2和3）。（目标4）建议使用数学建模来提供可测试的假设，并将生理研究的结果概念化。我们的假设是，我们将能够描述特定的SCN内网络活动与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.