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Authors & Affiliations
Joana Covelo, Leonardo Dalla Porta, Jose Manuel Sanchez-Sanchez, Arnau Manasanch, Rita M. Robles, Roman Arango, Emili Ballester-Balaguer, Maria V. Sanchez-Vives
Abstract
The different behavioral states inherent to the wake-sleep cycle are reflected in the electrical activity of the cerebral cortex. Slow-wave sleep (SWS) and deep anesthesia are dominated by high amplitude slow-wave oscillations (SWO, < 1 Hz). With the increase in arousal, desynchronization and low-amplitude fast rhythms arise. While SWS and wakefulness dynamics have been comprehensively described, their transition remains relatively unexplored. Tort-Colet et al (2021) previously reported the emergence of an intermediate brain state, the microarousal brain state, characterized by the rhythmic alternation between periods of synchronous (~2Hz oscillations) and asynchronous activity (microarousals). This meta-rhythm was observed in vivo during anesthesia fade-out in rats and was attributed to a brainstem input providing periodic modulation of cortical excitability. Here, we investigated the transition from SWO to a desynchronized state in the local cortical circuit in vitro. To do so, we applied carbachol and norepinephrine to cortical slices spontaneously expressing SWO (Barbero-Castillo et al, 2021). Under these conditions, we observed, as in vivo, a transitional state with a meta-rhythm which was alike the microarousal state. The spontaneous emergence of the microarousal state in an isolated cortical network suggests that recurrent cortical circuits have the necessary mechanisms in the absence of external input. Furthermore, we demonstrated that microarousals relied on muscarinic acetylcholine receptors, particularly M2. Our results contribute to a novel understanding of the microarousal state as a property of the local cortical network and support the pivotal role of muscarinic receptors in cortical state transitions. Funding: MSCA-ITN-ETNH2020-860563, META-BRAIN-GA-101130650, ERCSyG101071900.