Intrinsic regulation of spatiotemporal organization within the suprachiasmatic nucleus

Abstract

The mammalian pacemaker in the suprachiasmatic nucleus (SCN) contains a population of neural oscillators capable of sustaining cell-autonomous rhythms in gene expression and electrical firing. A critical question for understanding pacemaker function is how SCN oscillators are organized into a coherent tissue capable of coordinating circadian rhythms in behavior and physiology. Here we undertake a comprehensive analysis of oscillatory function across the SCN of the adult PER2::LUC mouse by developing a novel approach involving multi-position bioluminescence imaging and unbiased computational analyses. We demonstrate that there is phase heterogeneity across all three dimensions of the SCN that is intrinsically regulated and extrinsically modulated by light in a region-specific manner. By investigating the mechanistic bases of SCN phase heterogeneity, we show for the first time that phase differences are not systematically related to regional differences in period, waveform, amplitude, or brightness. Furthermore, phase differences are not related to regional differences in the expression of arginine vasopressin and vasoactive intestinal polypeptide, two key neuropeptides characterizing functionally distinct subdivisions of the SCN. The consistency of SCN spatiotemporal organization across individuals and across planes of section suggests that the precise phasing of oscillators is a robust feature of the pacemaker important for its function. Citation: Evans JA, Leise TL, Castanon-Cervantes O, Davidson AJ (2011) Intrinsic Regulation of Spatiotemporal Organization within the Suprachiasmatic Nucleus. PLoS ONE 6(1): e15869. doi:10.1371/journal.pone.0015869 Editor: Shin Yamazaki, Vanderbilt University, United States of America Received October 4, 2010; Accepted December 3, 2010; Published January 7, 2011 Copyright:  2011 Evans et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by NINDS/NIH grant U54NS060659, NCI/NIH grant P20CA132389, NCMHD/NIH grant S21MD000101, NCRR/NIH grant G12- RR03034, the Georgia Research Alliance, and the NSF Center for Behavioral Neuroscience. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: adavidson@msm.edu

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