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Circadian Biology at the Supra-Organismal Level

$386,782R01FY2012GMNIH

Univ Of Massachusetts Med Sch Worcester, Worcester MA

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Abstract

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.

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