Deficient synaptic neurotransmission results in a persistent sleep-like cortical activity across vigilance states in mice

Guillaumin, MCC; Harding, CD; Krone, LB; Yamagata, T; Kahn, MC; Blanco-Duque, C; Banks, GT; Achermann, P; Diniz Behn, C; Nolan, PM; Peirson, SN; Vyazovskiy, VV

Neuroscience & Neuroimaging Research Collection

Journal article

Deficient synaptic neurotransmission results in a persistent sleep-like cortical activity across vigilance states in mice

Abstract:: Growing evidence suggests that brain activity during sleep, as well as sleep regulation, are tightly linked with synaptic function and network excitability at the local and global levels. We previously reported that a mutation in synaptobrevin 2 (Vamp2) in restless (rlss) mice results in a marked increase of wakefulness and suppression of sleep, in particular REM sleep (REMS), as well as increased consolidation of sleep and wakefulness. In this study, using finer-scale in vivo electrophysiology recordings, we report that spontaneous cortical activity in rlss mice during NREM sleep (NREMS) is characterized by an occurrence of abnormally prolonged periods of complete neuronal silence (OFF-periods), often lasting several seconds, similar to the burst suppression pattern typically seen under deep anesthesia. Increased incidence of prolonged network OFF-periods was not specific to NREMS but also present in REMS and wake in rlss mice. Slow-wave activity (SWA) was generally increased in rlss mice relative to controls, while higher frequencies, including theta-frequency activity, were decreased, further resulting in diminished differences between vigilance states. The relative increase in SWA after sleep deprivation was attenuated in rlss mice, suggesting either that rlss mice experience persistently elevated sleep pressure or, alternatively, that the intrusion of sleep-like patterns of activity into the wake state attenuates the accumulation of sleep drive. We propose that a deficit in global synaptic neurotransmitter release leads to "state inertia," reflected in an abnormal propensity of brain networks to enter and remain in a persistent "default state" resembling coma or deep anesthesia.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Guillaumin, M. C. C., Harding, C. D., Krone, L. B., Yamagata, T., Kahn, M. C., Blanco-Duque, C., Banks, G. T., Achermann, P., Diniz Behn, C., Nolan, P. M., Peirson, S. N., & Vyazovskiy, V. V. (2025). Deficient synaptic neurotransmission results in a persistent sleep-like cortical activity across vigilance states in mice. Current Biology, 35(8), 1716–1729.

MLA Style

Guillaumin, MCC, et al. “Deficient Synaptic Neurotransmission Results in a Persistent Sleep-like Cortical Activity across Vigilance States in Mice.” Current Biology, vol. 35, no. 8, 2025, pp. 1716–29.

Chicago Style

Guillaumin, MCC, CD Harding, LB Krone, et al. 2025. “Deficient Synaptic Neurotransmission Results in a Persistent Sleep-like Cortical Activity across Vigilance States in Mice.” Current Biology 35 (8): 1716–29.
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