Causal role of persistent neural activity in the mouse medial prefrontal cortex in promotion of wakefulness

During wakefulness, cortical neurons fire tonically and asynchronously to constantly support ongoing cognitive functions, whereas they show synchronized cessation of firing, so called 'OFF periods', during NREM sleep. Previous studies reported that cortical neurons start showing local OFF periods even in awake animals as sleep pressure builds up during the course of sleep deprivation. However, spatio-temporal dynamics of OFF periods across the cerebral cortex during prolonged wakefulness remained unknown. In this study, our extracellular recording in free-behaving mice showed that prolonged wakefulness causes neuronal firing lapses in the medial prefrontal cortex (mPFC) but not in motor cortex, suggesting the importance of mPFC in maintaining cognition during wakefulness. We next examined cortical area-specific effects of sustained neural activation on vigilance states. Chemogenetic activation of excitatory neurons in mPFC, but not in motor or sensory cortex, promoted wakefulness. Additionally, chemogenetic inhibition of mPFC reduced time spent in wakefulness, further supporting the causal role of mPFC in wakefulness.