Local and niche-adapted sleep regulatory mechanisms encompass the holobiont condition

We posit that organism sleep is regulated from the interactions between two semi-autonomous regulatory systems, the classic sleep/wake regulatory circuits and a local cell activity-driven system. Sleep regulatory circuits mold local sleep into a species' niche but are not required for sleep. In contrast, local sleep mechanisms initiate sleep-like states in small networks and are responsive to microbial pattern recognition receptors. Local sleep-like phenomena manifest in brain in vivo and in vitro. Sleep regulatory substances e.g., cytokines and adenosine, are released by cell activity and as such provide an index of neural network activity. They are evolutionary ancient molecules existing prior to the evolution of complex vertebrate sleep. Further, bacterial cell wall components can initiate sleep in insomniac mammals lacking key hypothalamic regulatory circuits, suggesting our ancient holobiont condition underlies sleep regulation. We review how interleukin-1 promotes sleep/sleep-like states at various tissue organization levels. We provide a basis for understanding sleep as an emergent property of cellular networks and a process beginning at the cellular level and progressing as modified by multiple physiological regulatory circuits to whole animal sleep. We conclude; sleep mechanisms are shared across various levels of tissue organization and are part of interspecies regulatory networks.