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Mammalian Rest/Activity Patterns Explained by Physiologically Based Modeling

Circadian rhythms are fundamental to life. In mammals, these rhythms are generated by pacemaker neurons in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN is remarkably consistent in structure and function between species, yet mammalian rest/activity patterns are extremely diverse, in...

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Autores principales: Phillips, A. J. K., Fulcher, B. D., Robinson, P. A., Klerman, E. B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764015/
https://www.ncbi.nlm.nih.gov/pubmed/24039566
http://dx.doi.org/10.1371/journal.pcbi.1003213
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author Phillips, A. J. K.
Fulcher, B. D.
Robinson, P. A.
Klerman, E. B.
author_facet Phillips, A. J. K.
Fulcher, B. D.
Robinson, P. A.
Klerman, E. B.
author_sort Phillips, A. J. K.
collection PubMed
description Circadian rhythms are fundamental to life. In mammals, these rhythms are generated by pacemaker neurons in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN is remarkably consistent in structure and function between species, yet mammalian rest/activity patterns are extremely diverse, including diurnal, nocturnal, and crepuscular behaviors. Two mechanisms have been proposed to account for this diversity: (i) modulation of SCN output by downstream nuclei, and (ii) direct effects of light on activity. These two mechanisms are difficult to disentangle experimentally and their respective roles remain unknown. To address this, we developed a computational model to simulate the two mechanisms and their influence on temporal niche. In our model, SCN output is relayed via the subparaventricular zone (SPZ) to the dorsomedial hypothalamus (DMH), and thence to ventrolateral preoptic nuclei (VLPO) and lateral hypothalamus (LHA). Using this model, we generated rich phenotypes that closely resemble experimental data. Modulation of SCN output at the SPZ was found to generate a full spectrum of diurnal-to-nocturnal phenotypes. Intriguingly, we also uncovered a novel mechanism for crepuscular behavior: if DMH/VLPO and DMH/LHA projections act cooperatively, daily activity is unimodal, but if they act competitively, activity can become bimodal. In addition, we successfully reproduced diurnal/nocturnal switching in the rodent Octodon degu using coordinated inversions in both masking and circadian modulation. Finally, the model correctly predicted the SCN lesion phenotype in squirrel monkeys: loss of circadian rhythmicity and emergence of ∼4-h sleep/wake cycles. In capturing these diverse phenotypes, the model provides a powerful new framework for understanding rest/activity patterns and relating them to underlying physiology. Given the ubiquitous effects of temporal organization on all aspects of animal behavior and physiology, this study sheds light on the physiological changes required to orchestrate adaptation to various temporal niches.
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spelling pubmed-37640152013-09-13 Mammalian Rest/Activity Patterns Explained by Physiologically Based Modeling Phillips, A. J. K. Fulcher, B. D. Robinson, P. A. Klerman, E. B. PLoS Comput Biol Research Article Circadian rhythms are fundamental to life. In mammals, these rhythms are generated by pacemaker neurons in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN is remarkably consistent in structure and function between species, yet mammalian rest/activity patterns are extremely diverse, including diurnal, nocturnal, and crepuscular behaviors. Two mechanisms have been proposed to account for this diversity: (i) modulation of SCN output by downstream nuclei, and (ii) direct effects of light on activity. These two mechanisms are difficult to disentangle experimentally and their respective roles remain unknown. To address this, we developed a computational model to simulate the two mechanisms and their influence on temporal niche. In our model, SCN output is relayed via the subparaventricular zone (SPZ) to the dorsomedial hypothalamus (DMH), and thence to ventrolateral preoptic nuclei (VLPO) and lateral hypothalamus (LHA). Using this model, we generated rich phenotypes that closely resemble experimental data. Modulation of SCN output at the SPZ was found to generate a full spectrum of diurnal-to-nocturnal phenotypes. Intriguingly, we also uncovered a novel mechanism for crepuscular behavior: if DMH/VLPO and DMH/LHA projections act cooperatively, daily activity is unimodal, but if they act competitively, activity can become bimodal. In addition, we successfully reproduced diurnal/nocturnal switching in the rodent Octodon degu using coordinated inversions in both masking and circadian modulation. Finally, the model correctly predicted the SCN lesion phenotype in squirrel monkeys: loss of circadian rhythmicity and emergence of ∼4-h sleep/wake cycles. In capturing these diverse phenotypes, the model provides a powerful new framework for understanding rest/activity patterns and relating them to underlying physiology. Given the ubiquitous effects of temporal organization on all aspects of animal behavior and physiology, this study sheds light on the physiological changes required to orchestrate adaptation to various temporal niches. Public Library of Science 2013-09-05 /pmc/articles/PMC3764015/ /pubmed/24039566 http://dx.doi.org/10.1371/journal.pcbi.1003213 Text en © 2013 Phillips et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Phillips, A. J. K.
Fulcher, B. D.
Robinson, P. A.
Klerman, E. B.
Mammalian Rest/Activity Patterns Explained by Physiologically Based Modeling
title Mammalian Rest/Activity Patterns Explained by Physiologically Based Modeling
title_full Mammalian Rest/Activity Patterns Explained by Physiologically Based Modeling
title_fullStr Mammalian Rest/Activity Patterns Explained by Physiologically Based Modeling
title_full_unstemmed Mammalian Rest/Activity Patterns Explained by Physiologically Based Modeling
title_short Mammalian Rest/Activity Patterns Explained by Physiologically Based Modeling
title_sort mammalian rest/activity patterns explained by physiologically based modeling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764015/
https://www.ncbi.nlm.nih.gov/pubmed/24039566
http://dx.doi.org/10.1371/journal.pcbi.1003213
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