Temporal Association Cortex Gates Sound-Evoked Arousal from NREM Sleep

Sound-evoked wakefulness from sleep is crucial in daily life, yet its neural mechanisms remain poorly understood. It is found that CaMKIIα+ neurons in the temporal association cortex (TeA) of mice are not essential for natural awakening from sleep. However, optogenetic activation of these neurons reliably induces wakefulness from non-rapid eye movement (NREM) sleep but not from rapid eye movement (REM) sleep. In vivo electrophysiological and calcium recordings further demonstrated that TeA neurons are monotonically tuned to sound intensity but not frequency. More importantly, it is found that the activity of CaMKIIα+ neurons in TeA can gate sound-evoked arousal from NREM sleep, which is further confirmed by optogenetic manipulations. Further investigation reveals that the baseline excitability of TeA CaMKIIα+ neurons and the delta oscillations in the electroencephalogram are particularly important in regulating the evoked activity of TeA neurons. Anatomical and functional screening of downstream targets of TeA reveals that excitatory projections from TeA glutamatergic neurons to glutamatergic neurons in the basolateral/lateral amygdala are critical for modulating sound-evoked arousal from NREM sleep. These findings uncover a top-down regulatory circuit that selectively governs sound-evoked arousal from NREM sleep, with the TeA functioning as a key connecting cortex to subcortical regions.