Impact of NPAS2 on mPFC dopamine synthesis and nap behavior

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◆ 논문 초록 (Abstract)

The biological basis of the afternoon nap, a widespread yet poorly understood phenomenon, has remained elusive. Here we identify NPAS2, among core circadian regulators, as a sex-independent determinant of the nap behavior in mice. Specifically, medial prefrontal cortex (mPFC)-expressed NPAS2 orchestrates nap regulation through circadian modulation of local dopaminergic activity. We demonstrate that tyrosine hydroxylase-positive (TH+) neurons in mPFC exhibit time-of-day dependent wake-promoting activity, showing minimal excitation precisely during nap hours. Mechanistically, NPAS2 achieves this circadian suppression through a POU2F2-TH regulatory pathway: 1) transcriptional activation of the transcription repressor POU2F2, and 2) consequent downregulation of TH expression (a rate-limiting enzyme for dopamine synthesis) and dopamine production in mPFC TH+ neurons. These findings establish an endogenous circadian mechanism where mPFC NPAS2 periodically inhibits wake-promoting dopaminergic activity to drive nap behavior, providing fundamental insights into the neural and molecular regulation of nap biology.

◆ 원문 정보
저자: Guo L, Cen H, Huang Y, Li Z, Zeng K et al.
저널: Nat Commun
연도: 2026
DOI: 10.1038/s41467-026-70424-0

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