Mammalian Rest/Activity Patterns Explained by Physiologically Based Modeling

Abstract

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.

Exponential state transition dynamics in the rest–activity architecture of patients with bipolar disorder

“…We found a bimodal distribution in the rest–activity transition series during the rest phase, in keeping with models for sleep–wake architecture in healthy controls . The multi‐exponential pattern suggests multiple control points, possibly consistent with findings related to multiple wake‐ and sleep‐promoting systems in the mammalian brain .…”

Chronotype, class times, and academic achievement of university students

“…Different animal species align their activity rhythms with the daily cycle of light and darkness in diverse manners, the extremes of this continuum being represented by fully diurnal and nocturnal species (Bennie et al, 2014;Phillips et al, 2013;Refinetti, 2008). There is also variability within each species, the extent of variability being speciesdependent (Refinetti et al, 2016).…”

Distribution of histaminergic neuronal cluster in the rat and mouse hypothalamus

“…Pe is known for signal transduction in hypoxia (Huang et al, 2007), chronic mild stress (Kim et al, 2003), galanin (Takatsu et al, 2001), hypothalamic-pituitary-gonadal axis via somatostatin by GABAA (Bingaman et al, 1994;Llorens-cortes et al, 1992), and thyrotropin-releasing hormone by the glucocorticoid receptor (Cintra et al, 1990), respectively. The Spa has substantial roles in the relayed pathway from the suprachiasmatic nucleus (SCN) to DM with participation of orexin neurons (Nakamura et al, 2008;Schwartz et al, 2009;Yoshida et al, 2006) and integration of circadian rhythms (Phillips et al, 2013;Saper et al, 2005). DM, receiving dense efferents from SCN via Spa, is now noted for the critical role in the central regulation of the brown adipose tissues (BAT) for energy homeostasis in mammals (Kataoka et al, 2014;Nakamura and Morrison, 2011), particularly via central leptin signaling (Enriori et al, 2011;Rezai-Zadeh et al, 2014).…”