A brainstem circuit regulating anxiety with slow-wave sleep

Sleep disturbances are commonly linked with and constitute fundamental characteristics of anxiety disorders. However, the effects of actively increased sleep, especially slow wave sleep (SWS), after social defeat stress, on emotion regulation remain unexplored. By inducing time-locked SWS in mice by optogenetically stimulating the SWS promoting center in Vgat-ChR2-eYFP mice, we provide a direct approach to analyze the influences of SWS on anxiety-like behavior. Here we report that SWS induced by photostimulation immediately after social defeat prevents the development of anxiety disorder. We also identify that the brainstem SWS promoting center as a locus required for the anxiolysis of SWS. Through the combinatorial use of genetics and viral tracing, we demonstrate that the brainstem circuit inhibitor neurons monosynaptically innervated the lateral parabrachial nucleus, leading to the regulation of anxiety-like behaviors or wake-sleep transition. Activation of this pathway promoted the transition from wakefulness to SWS. In contrast, inhibition of this pathway facilitated anxiogenic effects. In conclusion, our results uncover an essential brainstem circuit that governs both sleep and anxiety. This provides a potential mechanistic explanation for the clinical observations in patients with anxiety disorders who also suffer from insomnia, and offers a potential therapeutic approach for anxiety disorder.