Ablation of Ventral Midbrain/Pons GABA Neurons Induces Mania-like Behaviors with Altered Sleep Homeostasis and Dopamine D₂R-mediated Sleep Reduction

Individuals with the neuropsychiatric disorder mania exhibit hyperactivity, elevated mood, and a decreased need for sleep. The brain areas and neuronal populations involved in mania-like behaviors, however, have not been elucidated. In this study, we found that ablating the ventral medial midbrain/pons (VMP) GABAergic neurons induced mania-like behaviors in mice, including hyperactivity, anti-depressive behaviors, reduced anxiety, increased risk-taking behaviors, distractibility, and an extremely shortened sleep time. Strikingly, these mice also showed no rebound sleep after sleep deprivation, suggesting abnormal sleep homeostatic regulation. Dopamine D₂ receptor deficiency largely abolished the sleep reduction induced by ablating the VMP GABAergic neurons without affecting the hyperactivity and anti-depressive behaviors. Our data demonstrate that VMP GABAergic neurons are involved in the expression of mania-like behaviors, which can be segregated to the short-sleep and other phenotypes on the basis of the dopamine D₂ receptors.