BIOLOGICAL RHYTHMS, PLASTICITY AND BEHAVIOR

描述(改编自申请人的摘要)：解除同步 由正常睡眠-觉醒周期的变化引起的正常昼夜节律功能， 不规律的工作模式或各种疾病状况都会对 影响生产效率，增加事故风险，影响 情绪/心理状态。糖尿病治疗方法的研究进展 改善昼夜节律失同步性的衰弱作用在于 了解内源性激素调节的神经学基础 昼夜节律。拟议研究的总体目标是 描述特定细胞表面成分在调节中的作用 昼夜节律时钟内的细胞间相互作用 下丘脑前部视交叉上核(SCN)。这个 聚唾液酸化NCAM(PSA-NCAM)是细胞表面起关键作用的成分 在神经发生中的作用，并保留在成人大脑中 具有神经可塑性的潜力。最近ITS的演示 SCN细胞的强劲表达导致了一种假设，即类似胚胎的 塑料形态重排可能对生物钟很重要 功能，例如它每天被光线重置的能力。这个 因此，拟议的研究旨在研究PSA-NCAM的作用(S 在SCN中使用生化、形态和行为终点。我们 将利用成年大脑中缺乏PSA-NCAM的转基因小鼠和 体内特异性地从NCAM中去除PSA的酶(Endo N)。我们会 首先在光镜和电子显微镜水平上确定哪些细胞 SCN表达PSA-NCAM以及其是否有每日波动 表情。然后我们将评估PSA-NCAM缺失对 昼夜运动节律的计时特征，包括 节奏的产生和夹带。最后，我们将检查以下方面的影响 PSA去除对SCN细胞-细胞相互作用形态指标的影响，包括 突触和神经对位的变化。这些研究的结果将 提供对细胞间通信动态的重要洞察力 哺乳动物的SCN昼夜节律钟。

DESCRIPTION (Adapted from applicant's abstract): Desynchronization of normal circadian functions induced by shifts in the normal sleep-wake cycle, irregular work patterns or various disease conditions is known to adversely affect productivity, increase the risks of accident and affect emotional/psychological state. Progress towards developing treatments for ameliorating the debilitating effects of circadian desynchrony lies in understanding the neurological basis for the regulation of endogenous circadian rhythms. The broad goal of the proposed studies is to characterize the roles of specific cell surface components in regulating cell-cell interactions within the circadian clock located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. The polysialylated NCAM (PSA-NCAM) is a cell surface component which plays key roles in neurogenesis and is retained in regions of the adult brain that have the potential for neural plasticity. The recent demonstration of its robust expression by SCN cells had led to the hypothesis that embryonic-like plastic morphological rearrangements may be important to circadian clock function, such as its ability to be reset on a daily basis by light. The proposed studies, therefore, are designed to study the role(s) of PSA-NCAM in the SCN using biochemical, morphological and behavioral endpoints. We will utilize transgenic mice that lack PSA-NCAM in the adult brain and an enzyme (endo N) that specifically removes PSA from NCAM in vivo. We will first determine at the light- and electron-microscopic levels which cells in the SCN express PSA-NCAM and whether there are daily fluctuations in its expression. We will then assess the effects of PSA-NCAM deletion on time-keeping characteristics of the circadian locomotor rhythm, including rhythm generation and entrainment. Finally, we will examine the effects of PSA removal on morphological indices of SCN cell-cell interaction, including changes in synapses and neural appositions. Results from these studies will provide important insight into the dynamics of cell-cell communication in the mammalian SCN circadian clock.