Ba, W., Nollet, M., Yin, C., Yu, X., Wong, S., Miao, A., Beckwith, E., Harding, E.C., Ma, Y., Yustos, R., Vyssotski, A., Wisden, W.C., & Franks, N.P. (2024). A REM-active basal ganglia circuit that regulates anxiety. Current Biology, 34, 1–14.
Abstract
Rapid eye movement (REM) sleep has been hypothesized to promote emotional resilience, but any neuronal
circuits mediating this have not been identified. We find that in mice, somatostatin (Som) neurons in the entopeduncular nucleus (EPSom)/internal globus pallidus are predominantly active during REM sleep. This
unique REM activity is both 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 scheme to periodically inhibit the LHb over 4 days selectively removed a
significant amount of cumulative REM sleep. Chronic, but not acute, REM reduction correlated with mice
becoming anxious and more sensitive to aversive stimuli. Therefore, we suggest that cumulative REM sleep,
in part generated by the EP / LHb / VTA circuit identified here, could contribute to stabilizing reactions to
habitual aversive stimuli.
Keywords
basal ganglia; habenula; ventral tegmental area; rapid eye movement sleep; non-rapid eye movement sleep; somatostatin neurons; Vglut2 neurons; anxiety; defensive behavior; emotion
