Chimera Analysis of the Clock Mutation in Mice Shows that Complex Cellular Integration Determines Circadian Behavior

Low-Zeddies, Sharon S.; Takahashi, Joseph S.

doi:10.1016/s0092-8674(01)00294-x

Cited by 137 publications

(112 citation statements)

References 68 publications

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“…Also, we found that individual variability in behavioural activity duration was related to properties evident at the population level, which is consistent with recent work investigating seasonal encoding within the SCN [29][30][31][32][33][34]. Of note, previous research also indicates a strong link between behavioural period and SCN function [35,36], but we were unable to address this issue here because our mice did not display marked variability in behavioural period.…”

Section: Discussionsupporting

confidence: 89%

Neural correlates of individual differences in circadian behaviour

et al. 2015

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Daily rhythms in mammals are controlled by the circadian system, which is a collection of biological clocks regulated by a central pacemaker within the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. Changes in SCN function have pronounced consequences for behaviour and physiology; however, few studies have examined whether individual differences in circadian behaviour reflect changes in SCN function. Here, PERIOD2::LUCIFERASE mice were exposed to a behavioural assay to characterize individual differences in baseline entrainment, rate of re-entrainment and free-running rhythms. SCN slices were then collected for ex vivo bioluminescence imaging to gain insight into how the properties of the SCN clock influence individual differences in behavioural rhythms. First, individual differences in the timing of locomotor activity rhythms were positively correlated with the timing of SCN rhythms. Second, slower adjustment during simulated jetlag was associated with a larger degree of phase heterogeneity among SCN neurons. Collectively, these findings highlight the role of the SCN network in determining individual differences in circadian behaviour. Furthermore, these results reveal novel ways that the network organization of the SCN influences plasticity at the behavioural level, and lend insight into potential interventions designed to modulate the rate of resynchronization during transmeridian travel and shift work.

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Section: Discussionsupporting

confidence: 89%

Neural correlates of individual differences in circadian behaviour

et al. 2015

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“…In particular, the number of cells and the proportions of different cell types affect period and the stability of rhythms [8,19,12,18]. If functionally different cells are produced at different times, as the present results indicate [4], then small changes in the duration or intensity of proliferation of SCN progenitors at different times in development could be one source of variation (both within and between species) in the overall function of the nucleus.…”

Section: Discussionmentioning

confidence: 56%

Development of the mouse suprachiasmatic nucleus: Determination of time of cell origin and spatial arrangements within the nucleus

Kabrita

Davis

2008

Brain Research

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The suprachiasmatic nucleus (SCN) in mammals functions as the principal circadian pacemaker synchronizing diverse physiological and behavioral processes to environmental stimuli. It consists of heterogeneous populations of cells with unique spatial organization that can vary among species, but are commonly discussed within a framework of two principal regions, the ventrolateral or dorsomedial halves of the nucleus or in other instances the core and shell. In both hamsters and rats, cells of different SCN regions have been shown to have different developmental histories. Using bromodeoxyuridine as a marker of cell division, the present study investigated the time of SCN cell origin in mice (C57BL/6) and their settling patterns within the nucleus. Results show that SCN cytogenesis occurs between embryonic days 12 and 15 and is complete 5 days prior to birth. Cells born on embryonic day 12 are mainly confined to a ventrolateral region of the mid-SCN, whereas cells produced later on embryonic days 13.5 and 14.5 form a cap around the cells produced first and extend into the posterior and anterior ends of the nucleus. These results suggest an ordered spatiotemporal program of SCN cytogenesis whereby a mid-SCN core is born first followed by a surrounding shell of later-born cells. Variation in cytogenesis could affect the relative sizes of different SCN regions and, thereby, affect its function. The relative contributions of a highly ordered program of cytogenesis and intercellular interactions after post-mitotic cells leave the germinal epithelium remain to be determined.

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“…From the invertebrate studies (for review see Dunlap 1996), rhythms result from transcriptional feedback loops in which the mRNA and protein products of circadian genes oscillate in abundance, with the mRNA and protein peaks offset. Mutant circadian-clock genes have been identified in hamsters and mice, and similar genetics may affect human rhythms (Ralph and Menaker 1988;Vitaterna et al 1994;Low-Zeddies and Takahashi 2001;Panda et al 2002a,b). Choline acetyltransferase and glutamate decarboxylase show circadian fluctuations in human subjects (Perry et al 1977), so the time of day at which death occurs may be pertinent (Lausson et al 1989).…”

Section: Circadian and Circannual Rhythmsmentioning

confidence: 99%

Biochemical and molecular studies using human autopsy brain tissue

Hynd

Lewohl

Scott

et al. 2003

Journal of Neurochemistry

221

171

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The use of human brain tissue obtained at autopsy for neurochemical, pharmacological and physiological analyses is reviewed. RNA and protein samples have been found suitable for expression profiling by techniques that include RT-PCR, cDNA microarrays, western blotting, immunohistochemistry and proteomics. The rapid development of molecular biological techniques has increased the impetus for this work to be applied to studies of brain disease. It has been shown that most nucleic acids and proteins are reasonably stable postmortem. However, their abundance and integrity can exhibit marked intra-and intercase variability, making comparisons between case-groups difficult. Variability can reveal important functional and biochemical information. The correct interpretation of neurochemical data must take into account such factors as age, gender, ethnicity, medicative history, immediate ante-mortem status, agonal state and post-mortem and post-autopsy intervals. Here we consider issues associated with the sampling of DNA, RNA and proteins using human autopsy brain tissue in relation to various ante-and postmortem factors. We conclude that valid and practical measures of a variety of parameters may be made in human brain tissue, provided that specific factors are controlled.

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Chimera Analysis of the Clock Mutation in Mice Shows that Complex Cellular Integration Determines Circadian Behavior

Cited by 137 publications

References 68 publications

Neural correlates of individual differences in circadian behaviour

Neural correlates of individual differences in circadian behaviour

Development of the mouse suprachiasmatic nucleus: Determination of time of cell origin and spatial arrangements within the nucleus

Biochemical and molecular studies using human autopsy brain tissue

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