Non-rapid eye movement sleep and isoflurane-induced anesthesia show divergent subcortical connectivity patterns during transition phases in mice

Study Objectives Neural dynamics underlying anesthesia-induced unconsciousness are not fully understood. Given the parallels between natural sleep and anesthesia-induced unconsciousness, it becomes imperative to understand the neuronal mechanisms behind these two distinct, yet seemingly interconnected states. This study investigated the interplay between sleep/ wake promoting nuclei during WAKE / NREM-sleep (NREMS) transitions, and the reversible loss and recovery of responsiveness (LOR/ROR) induced by isoflurane. Methods Local field potentials (LFP) were recorded from the ventrolateral preoptic nucleus (VLPO) and locus coeruleus (LC) in mice alongside chronic EEG-recordings. After baseline recordings, a slow induction regime of isoflurane anesthesia followed. Functional connectivity between VLPO and LC during NREMS, WAKE, LOR and ROR was studied using coherence, inter site phase clustering and Granger causality analyses. Results LFP data revealed an increase in coherence between VLPO and LC during NREMS, a decrease during WAKE. Coherence decreased after LOR. During ROR coherence did not change. Phase clustering between VLPO and LC increased during NREMS, decreased during WAKE, while across LOR/ROR transitions did not vary. Granger between VLPO and LC during WAKE/NREM transitions demonstrated bidirectional influences of the two nuclei. VLPO Granger caused LC during NREMS. In the slow-wave frequency, the Granger index from LC to VLPO decreased during NREMS, while after ROR, the Granger index from VLPO to LC increased. Conclusions The present study revealed functional connectivity patterns between VLPO and LC during sleep and isoflurane anesthesia, suggesting that these processes partly do not share similar functional connectivity patterns for the two nuclei.