Brainstem circuit for sickness-induced sleep.

Increased sleep induced by immune activation plays a crucial role in facilitating recovery from illness. However, the neural mechanisms underlying sickness-induced sleep remain poorly understood. Here, we identify a brainstem circuit originating in the nucleus of the solitary tract (NST) that mediates sickness-induced nonrapid eye movement (NREM) sleep. Using activity-dependent genetic labeling, we tagged NST neurons activated by lipopolysaccharide (LPS) injection and showed that their chemogenetic activation strongly promotes NREM sleep. These NST neurons project extensively to the parabrachial nucleus (PB), where LPS-activated neurons also promote NREM sleep. Fiber photometry recording of several wake-promoting neuromodulators using their biosensors showed that evoked norepinephrine release from locus coeruleus neurons is markedly reduced by either LPS injection or direct activation of NST or PB sickness neurons. These results suggest that sickness-induced NREM sleep is mediated in part by a brainstem circuit that regulates neuromodulator signaling.