Lack of Bmal1 leads to changes in rhythmicity and impairs motivation towards natural stimuli

Berbegal-Sáez, Paula; Gallego-Landin, Ines; Macía, Javier; Alegre Zurano, Laia; Castro Zavala, Adriana, 1988-; Welz, Patrick-Simon; Benitah, Salvador A.; Valverde Granados, Olga

doi:http://dx.doi.org/10.1098/rsob.240051

Lack of Bmal1 leads to changes in rhythmicity and impairs motivation towards natural stimuli

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Berbegal-Sáez P, Gallego-Landin I, Macía J, Alegre-Zurano L, Castro-Zavala A, Welz PS, et al. Lack of Bmal1 leads to changes in rhythmicity and impairs motivation towards natural stimuli. Open Biol. 2024 Jul;14(7):240051. DOI: 10.1098/rsob.240051

Abstract

Maintaining proper circadian rhythms is essential for coordinating biological functions in mammals. This study investigates the effects of daily arrhythmicity using Bmal1-knockout (KO) mice as a model, aiming to understand behavioural and motivational implications. By employing a new mathematical analysis based on entropy divergence, we identified disrupted intricate activity patterns in mice derived by the complete absence of BMAL1 and quantified the difference regarding the activity oscillation's complexity. Changes in locomotor activity coincided with disturbances in circadian gene expression patterns. Additionally, we found a dysregulated gene expression profile particularly in brain nuclei like the ventral striatum, impacting genes related to reward and motivation. Further investigation revealed that arrhythmic mice exhibited heightened motivation for food and water rewards, indicating a link between circadian disruptions and the reward system. This research sheds light on how circadian clock alterations impact the gene expression regulating the reward system and how this, in turn, can lead to altered seeking behaviour and motivation for natural rewards. In summary, the present study contributes to our understanding of how reward processing is under the regulation of circadian clock machinery.