Circadian Biology at the Supra-Organismal Level

描述（由申请人提供）：生理和行为的每日节律由内源性计时机制（昼夜节律“时钟”）控制。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需要同居者在相对较长的时间内进行直接的身体接触，但实验的问题是，记录日常活动的常用方法无法区分同一笼中单独动物的活动。我们目前的初步数据，我们相信打开新的机会，提出问题，并解决机制，在这个社会层面的时间组织。我们已经发现，共同饲养成对的金黄仓鼠或雌性实验室小鼠可以导致生物钟特性的变化（自由运行的昼夜节律周期，D）。我们还开发和测试了微型植入式装置，用于纵向记录个别啮齿动物的体温和一般运动活动。在本申请中，我们希望通过提出三个具体目标来利用这些进步。在目标1中，我们建议开发一个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的相位关系的函数，取决于车轮运行，表现出性别差异，并导致光夹带期间活动的相位或分布改变。在目标2中，我们试图暗示两个可能的因素-嗅觉和性腺激素-作为候选神经内分泌元素的通路参与社会线索转换成信号，最终影响振荡的主昼夜节律起搏器在视交叉上核（SCN）。在目标3中，我们开始研究雌性实验室小鼠中的社会时钟，询问组同步是否可以是D的同居相关变化的结果，以及同居结果如何受到野生型小鼠与行为缺陷的突变笼友的共同圈养的影响（时钟？19/？19，Avpr1atm1Dgen）. 公共卫生相关性：我们从我们的实验中学到的东西应该丰富我们的生物钟和动物群落的时间生物学的理解，也许提供未来的洞察力的昼夜节律系统的适应功能的合作和/或竞争的时间域。值得注意的是，人类，包括盲人，患有昼夜节律紊乱，我们对社会线索对昼夜节律系统的影响的研究最终可能导致非光方法的发展，以帮助这些人调整日常安排或更容易地转移到新的时间表，从而减少这些疾病的生理和心理后果。

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). PUBLIC HEALTH RELEVANCE: What we learn from our experiments should enrich our understanding of the circadian clock and the chronobiology of animal communities, perhaps providing future insights into the adaptive function of the circadian system for cooperation and/or competition in the temporal domain. Notably, humans, including blind individuals, suffer from circadian disorders, and our investigation of the effects of social cues on the circadian system could eventually lead to the development of non-photic approaches to help these individuals adjust to a daily schedule or more easily shift to a new one, thereby reducing the physiological and psychological consequences of these disorders.