A REM-active basal ganglia circuit that regulates anxiety

REM sleep has been hypothesized to promote emotional resilience, but no neuronal circuitsmediating this have been identified. We find that in mice, somatostatin (Som) neurons in theentopeduncular nucleus (EPSom)/internal globus pallidus are predominantly active during REMsleep. This unique REM activity is necessary and sufficient for maintaining normal REM sleep.Inhibiting or exciting EPSom neurons reduced or increased REM sleep duration, respectively.Activation of the sole downstream target of EPSom neurons, Vglut2 cells in the lateral habenula(LHb), increased sleep via the ventral tegmental area (VTA). A simple chemogenetic schemeto periodically inhibit the LHb over 4 days selectively removed a significant amount ofcumulative REM sleep. Chronic REM reduction correlated with mice becoming anxious andmore sensitive to aversive stimuli. Therefore, we suggest that REM sleep, in part generated bythe EP-LHb-VTA circuit identified here, could contribute to stabilizing reactions to habitualaversive stimuli.