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[Preprint]. 2023 Jun 28:2023.06.26.546624. [Version 1] doi: 10.1101/2023.06.26.546624

The circadian molecular clock in the suprachiasmatic nucleus is necessary but not sufficient for fear entrainment in the mouse

Ivana L Bussi, Miriam Ben-Hamo, Luis E Salazar Leon, Leandro P Casiraghi, Victor Y Zhang, Alexandra F Neitz, Jeffrey Lee, Joseph S Takahashi, Jeansok J Kim, Horacio O de la Iglesia
PMCID: PMC10327100  PMID: 37425771

Abstract

Nocturnal aversive stimuli presented to mice during eating and drinking outside of their safe nest can entrain circadian behaviors, leading to a shift toward daytime activity. We show that the canonical molecular circadian clock is necessary for fear entrainment and that an intact molecular clockwork in the suprachiasmatic nucleus (SCN), the site of the central circadian pacemaker, is necessary but not sufficient to sustain fear entrainment of circadian rhythms. Our results demonstrate that entrainment of a circadian clock by cyclic fearful stimuli can lead to severely mistimed circadian behavior that persists even after the aversive stimulus is removed. Together, our results support the interpretation that circadian and sleep symptoms associated with fear and anxiety disorders may represent the output of a fear-entrained clock.

One-Sentence Summary

Cyclic fearful stimuli can entrain circadian rhythms in mice, and the molecular clock within the central circadian pacemaker is necessary but not sufficient for fear-entrainment.

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