Role of the LC arousal promoting neurons in maintaining brain criticality across the sleep-wake cycle.

ABSTRACT

Sleep control depends on a delicate interplay among brain regions. This generates a complex temporal architecture with numerous sleep-stage transi-tions and intermittent fluctuations to micro-states and brief arousals within sleep stages. These temporal dynamics exhibit hallmarks of criticality, suggest-ing that tuning to criticality is essential for spontaneous sleep-stage and arousal transitions. However, how the brain maintains criticality remains not under-stood. Here, we investigate dynamics of θ- and δ-bursts during the sleep-wake cycle of rats (Sprague-Dawley, adult male) with lesion in the wake-promoting locus coeruleus (LC). We show that, in control rats, θ- and δ-bursts exhibit duality of power-law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, as well as power-law long-range tem-poral correlations (LRTC)-typical of non-equilibrium systems self-organizing at criticality. Further, consecutive θ- and δ-bursts durations are characterized by anti-correlated coupling, indicating a new class of self-organized critical- ity that emerges from underlying feedback between neuronal populations and brain areas involved in generating arousals and sleep states. In contrast, we uncover that LC lesion leads to alteration of θ- and δ-burst critical features, with change in duration distributions and correlation properties, and increase in θ-δ coupling. Notably, these LC-lesion effects are opposite to those observed for lesions in the sleep-promoting ventrolateral preoptic nucleus (VLPO). Our findings indicate that critical dynamics of θ- and δ-bursts arise from a bal-anced interplay of LC and VLPO, which maintains brain tuning to criticality across the sleep-wake cycle-a continuous non-equilibrium behavior in sleepSignificance statement Criticality has been associated with healthy brain function in both sleep and wake. However, how the sleep-wake control circuitry maintains criticality remains not un-derstood. Our analyses demonstrate that arousal promoting neurons in the LC play a key role in maintaining brain criticality across the sleep-wake cycle. The results show that lesions of the wake-promoting LC affect the critical dynamics of θ and δ bursts, altering duration distributions, correlation properties, and θ-δ coupling. The reported changes in criticality measures are opposite to those caused by lesions of the sleep-promoting VLPO. This suggests that feed-forward and feedback interactions among neuronal populations in the LC and VLPO are essential to maintain the brain tuned to criticality across the sleep-wake cycle.