Disruption of circadian rhythms, such as shift work and jet lag, are associated with negative physiological and behavioral outcomes, including changes in affective state, learning and memory, and cognitive function. The prefrontal cortex (PFC) is heavily involved in all of these processes. Many PFC-associated behaviors are time-of-day dependent, and disruption of daily rhythms negatively impacts these behavioral outputs. Yet how disruption of daily rhythms impacts the fundamental function of PFC neurons, and the mechanism(s) by which this occurs, remains unknown. Using a mouse model, we demonstrate that the activity and action potential dynamics of prelimbic PFC neurons are regulated by time-of-day in a sex specific manner. Further, we show that postsynaptic K⁺ channels play a central role in physiological rhythms, suggesting an intrinsic gating mechanism mediating physiological activity. Finally, we demonstrate that environmental circadian desynchronization alters the intrinsic functioning of these neurons independent of time-of-day. These key discoveries demonstrate that daily rhythms contribute to the mechanisms underlying the essential physiology of PFC circuits and provide potential mechanisms by which circadian disruption may impact the fundamental properties of neurons.

昼夜节律的紊乱，例如轮班工作和时差反应，与负面的生理和行为结果有关，包括情感状态、学习和记忆以及认知功能的变化。前额叶皮层 (PFC) 大量参与所有这些过程。许多与 PFC 相关的行为都依赖于一天中的时间，并且日常节律的中断会对这些行为输出产生负面影响。然而，日常节律的破坏如何影响 PFC 神经元的基本功能，以及这种情况发生的机制，仍然未知。使用小鼠模型，我们证明了前肢 PFC 神经元的活动和动作电位动态受一天中的时间以性别特定方式调节。此外，我们表明突触后 K ⁺通道在生理节律中起着核心作用，表明调节生理活动的内在门控机制。最后，我们证明环境昼夜节律去同步化会独立于一天中的时间改变这些神经元的内在功能。这些重要发现表明，日常节律有助于 PFC 电路基本生理学的潜在机制，并提供了昼夜节律中断可能影响神经元基本特性的潜在机制。