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

Author:

Berbegal-Sáez Paula1,Gallego-Landin Ines1,Macía Javier2,Alegre-Zurano Laia1,Castro-Zavala Adriana1,Welz Patrick-Simon3ORCID,Benitah Salvador A.45,Valverde Olga16ORCID

Affiliation:

1. Department of Medicine and Life Sciences (MELIS), Neurobiology of Behaviour Research Group (GReNeC-NeuroBio), Universitat Pompeu Fabra, Barcelona, Spain

2. Department of Medicine and Life Sciences (MELIS), Synthetic Biology for Biomedical Applications, Universitat Pompeu Fabra, Barcelona, Spain

3. Program in Cancer Research, Hospital del Mar Research Institute (IMIM), Barcelona, Spain

4. Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, Barcelon 08028, Spain

5. Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain

6. Neuroscience Research Program, Hospital del Mar Research Institute (IMIM), Barcelona, Spain

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.

Funder

Agencia Estatal de Investigación

Agència de Gestió d'Ajuts Universitaris i de Recerca

Ministerio de Sanidad, Política Social e Igualdad

Publisher

The Royal Society

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