Role of the LC arousal promoting neurons in maintaining brain criticality across the sleep-wake cycle
Sleep control depends on a delicate interplay among brain regions. This generates a complex temporal architecture with numerous sleep-stage transitions and intermittent fluctuations to micro-states and brief arousals within sleep stages. These temporal dynamics exhibit hallmarks of criticality, suggesting that tuning to criticality is essential for spontaneous sleep-stage and arousal transitions. However, how the brain maintains criticality remains not understood. 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 temporal 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 balanced interplay of LC and VLPO, which maintains brain tuning to criticality across the sleep-wake cycle—a continuous non-equilibrium behavior in sleep
Significance 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 understood. 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.
The authors declare no competing financial interests.
We acknowledge support from the W. M. Keck Foundation, National Institutes of Health (NIH Grant 1R01-HL098437), the US-Israel Binational Science Foundation (BSF Grant 2012219 and BSF Grant 2020020), the Office of Naval Research (ONR Grant ONR Grant 000141010078). FL acknowledges support from the European Union's Horizon research and innovation program under the Marie Sklodowska-Curie Grant Agreement No. 754411 and No. 101066790, from the Austrian Science Fund (FWF) (grant no. PT1013M03318), and from the NextGenerationEU through the grant TAlent in ReSearch@University of Padua - STARS@UNIPD (project BRAINCIP—Brain criticality and information processing).