Circadian Biology at the Supra-Organismal Level

描述(申请人提供)：生理和行为的日常节律由一种内源性的计时机制(生物钟)控制。除了光信号，社交线索可能在昼夜节律系统的功能中发挥重要作用。社会暗示的有效性可能需要同居者在相对较长的一段时间内保持直接的身体接触，但实验问题是，通常记录日常活动的方法无法区分关在同一笼子里的单个动物的活动。我们提供了初步数据，我们认为这些数据为在这一社会层面的临时组织中提出问题和解决机制提供了新的机会。我们已经发现，金黄仓鼠或雌性实验室小鼠共同居住会导致生物钟特性(自由奔跑的生物钟周期，D)的变化。我们还开发和测试了微型植入式设备，用于纵向记录个体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展。在目标1中，我们建议建立仓鼠同居的时间生物学，询问与同居相关的D的变化是否是同居者之间的相位关系的函数，取决于轮子的运行，表现出性别差异，并导致光携带期间活动的相或分布改变。在目标2中，我们试图将两个可能的因素--嗅觉和性腺激素--作为候选神经内分泌元件，参与将社会线索转化为信号，最终影响视交叉上核(SCN)主昼夜节律起搏器的振荡。在目标3中，我们开始研究雌性实验小鼠的社会时钟，询问群体同步是否可以是D同居相关变化的结果，以及野生型小鼠与行为有缺陷的突变笼友(Clock？19/？19，Avpr1atm1Dgen)共同居住对同居结果有何影响。 与公共健康相关：我们从我们的实验中学到的东西应该会丰富我们对生物钟和动物群的时间生物学的理解，也许会为未来提供对昼夜节律系统在时间域中合作和/或竞争的适应功能的洞察。值得注意的是，包括盲人在内的人类患有昼夜节律紊乱，我们对社交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，以帮助这些人适应每日时间表或更容易地转换到新的时间表，从而减少这些紊乱的生理和心理后果。

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.