The slow-acting G-protein G z defines the duration of circadian rest time

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Abstract

Duration of nightly rest is a trait that varies between individuals, influenced by a complex interplay between multiple genetic and environmental factors. The central circadian clock that orchestrates daily rhythm in behavior/sleep resides in the suprachiasmatic nucleus (SCN). Yet, how the SCN encodes the “length” of the circadian rest phase (ρ) remains an open question. Here we demonstrate that the unique G-protein-subtype Gz contributes to this process by sculpting the waveform of the circadian cAMP-PKA activity rhythm within the SCN. Genetic deletion and subsequent rescue of Gz expression reversibly altered the ρ duration, shifting it from ∼10 h in Gz +/+ mice to ∼7.5 h in Gz -/-; mice, accompanied by proportional changes in peak cAMP-PKA activity duration and transcriptome remodeling in the SCN. Notably, intra-SCN cAMP activation led to behavioral rest, with Gz specifically shaping this response without affecting 24-h rhythmicity. These findings suggest that the SCN is not merely a rhythm-generator, but actively allocates the ρ-rest period via Gz signaling.

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