A distributed auditory network mediated by pontine central gray underlies ultra-fast awakening in response to alerting sounds

Sleeping animals can be woken up rapidly by external threat signals, which is an essential defense mechanism for survival. However, neuronal circuits underlying the fast transmission of sensory signals for this process remain unclear. Here, we report in mice that alerting sound can induce rapid awakening within hundreds of milliseconds and that glutamatergic neurons in the pontine central gray (PCG) play an important role in this process. These neurons exhibit higher sensitivity to auditory stimuli in sleep than wakefulness. Suppressing these neurons results in reduced sound-induced awakening and increased sleep in intrinsic sleep/wake cycles, whereas their activation induces ultra-fast awakening from sleep and accelerates awakening from anesthesia. Additionally, the sound-induced awakening can be attributed to the propagation of auditory signals from the PCG to multiple arousal-related regions, including the mediodorsal thalamus, lateral hypothalamus, and ventral tegmental area. Thus, the PCG serves as an essential distribution center to orchestrate a global auditory network to promote rapid awakening. [Display omitted] •PCG glutamatergic neurons contribute to sound-induced rapid awakening•They exhibit higher sensitivity in sleep and modulate intrinsic sleep/wake states•Their activation induces ultra-fast awakening from NREM sleep•PCG transmits auditory signals to a multitude of arousal-related brain regions The ability to rapidly wake up from sleep upon threat signals is critical for animal survival. In this study, Wei et al. report that the pontine central gray (PCG) is a critical node of a fast-execution alerting system and globally broadcasts alerting auditory signals to a distributed brain network to promote awakening.