Circadian Biology at the Supra-Organismal Level

描述（由申请人提供）：生理和行为的日常节奏是由内源性计时机制（昼夜节律“时钟”）控制的。除了光信号，社会线索可能在昼夜节律系统的功能中发挥重要作用。社会线索的有效性可能要求同居动物在相当长的一段时间内进行直接的身体接触，但实验的问题是，通常记录日常活动的方法无法区分关在同一个笼子里的单个动物的活动。我们提出了初步的数据，我们认为这为提出问题和解决这种社会层面的时间组织机制提供了新的机会。我们发现，金仓鼠或雌性实验小鼠共同居住会导致生物钟特性的变化（自由运行的昼夜节律周期，D）。我们还开发并测试了用于纵向记录单个啮齿动物体温和一般运动活动的微型植入式设备。在本应用程序中，我们希望通过提出三个具体目标来利用这些进步。在Aim 1中，我们建议发展仓鼠同居的时间生物学，询问同居相关的D变化是否是同居者之间相位关系的函数，取决于车轮运行，表现出性别差异，并导致光携带期间活动的相位或分布的改变。在Aim 2中，我们试图暗示两种可能的因素——嗅觉和性腺激素——作为候选神经内分泌因子，参与将社会线索转导成最终影响视交叉上核（SCN）主昼夜节律起搏器振荡的信号通路。在Aim 3中，我们开始研究雌性实验室小鼠的社会时钟，询问群体同步是否可能是与同居相关的D变化的结果，以及与行为缺陷，突变的笼子伴侣共同居住的野生型小鼠如何影响同居结果(clock ?19/？19日,Avpr1atm1Dgen)。

DESCRIPTION (provided by applicant): Daily rhythms of physiology and behavior are governed by an endogenous timekeeping mechanism (a circadian "clock"). In addition to photic signals, social cues may play an important role in the function of the circadian system. The efficacy of social cues may require that cohabitants be in direct physical contact for a relatively long period of time, but the experimental problem has been that the usual methods of recording daily activity fail to distinguish the activities of individual animals housed together in the same cage. We present preliminary data that we believe open new opportunities to pose questions and address mechanisms at this social level of temporal organization. We have found that co-housing pairs of golden hamsters or female laboratory mice can result in a change in a circadian clock property (the free-running circadian period, D). We have also developed and tested miniature implantable devices for longitudinally recording body temperature and general locomotor activity in individual rodents. In this application, we wish to exploit these advances by proposing three specific aims. In Aim 1, we propose to develop a chronobiology of cohabitation in hamsters, asking if the cohabitation-associated change in D is a function of the phase relationship between cohabitants, depends on wheel running, exhibits a sex difference, and leads to an altered phase or distribution of activity during photic entrainment. In Aim 2, we seek to implicate two likely factors - olfaction and gonadal hormones - as candidate neuroendocrine elements in the pathways involved in transducing social cues into signals that ultimately affect the oscillation of the master circadian pacemaker in the suprachiasmatic nucleus (SCN). In Aim 3, we begin to investigate a social clock in female laboratory mice, asking if group synchronization can be a consequence of cohabitation-associated changes in D and how cohabitation outcome is affected by co- housing wild type mice with behaviorally-defective, mutant cage-mates (Clock ?19/?19, Avpr1atm1Dgen).