Pupil Size Coupling to Cortical States Protects the Stability of Deep Sleep via Parasympathetic Modulation

• Published in: Current biology 2018-02, Vol.28 (3), p.392-400.e3
• Main Authors: Yüzgeç, Özge, Prsa, Mario, Zimmermann, Robert, Huber, Daniel
• Format: Article
• Language: English
• Subjects: Animals; EEG; head fixed; infrared back-illumination pupillometry; Male; Mice; Mice, Inbred C57BL; mouse; Neurologic Examination - methods; parasympathetic; Pupil - physiology; pupil tracking; Reflex, Pupillary - physiology; sleep; sleep spindles; Sleep, Slow-Wave - physiology; ultra-slow oscillations; Wakefulness - physiology
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2017.12.049

During wakefulness, pupil diameter can reflect changes in attention, vigilance, and cortical states. How pupil size relates to cortical activity during sleep, however, remains unknown. Pupillometry during natural sleep is inherently challenging since the eyelids are usually closed. Here, we present a novel head-fixed sleep paradigm in combination with infrared back-illumination pupillometry (iBip) allowing robust tracking of pupil diameter in sleeping mice. We found that pupil size can be used as a reliable indicator of sleep states and that cortical activity becomes tightly coupled to pupil size fluctuations during non-rapid eye movement (NREM) sleep. Pharmacological blocking experiments indicate that the observed pupil size changes during sleep are mediated via the parasympathetic system. We furthermore found that constrictions of the pupil during NREM episodes might play a protective role for stability of sleep depth. These findings reveal a fundamental relationship between cortical activity and pupil size, which has so far been hidden behind closed eyelids. •Infrared back-illumination allows accurate pupillometry in sleeping mice•Brain activity and pupil diameter are tightly coupled during sleep•The parasympathetic system is the main driver of pupillary changes during NREM sleep•Pupillary constrictions might have a protective function to stabilize deep sleep Using infrared back-illumination pupillometry in head-fixed sleeping mice, Yüzgeç et al. show that pupil diameter is tightly coupled to cortical states during sleep. Pharmacological and light-stimulation experiments reveal that the pupillary constrictions are parasympathetically driven and might have a protective function to stabilize deep sleep.