Regulation of stress-induced sleep perturbations by dorsal raphe VGLUT3 neurons in male mice.

Exposure to stressors has profound effects on sleep that have been linked to serotonin (5-HT) neurons of the dorsal raphe nucleus (DR). However, the DR also comprises glutamatergic neurons expressing vesicular glutamate transporter type 3 (DR^VGLUT3), leading us to examine their role. Cell-type-specific tracing revealed that DR^VGLUT3 neurons project to brain areas regulating arousal and stress. We found that chemogenetic activation of DR^VGLUT3 neurons mimics stress-induced sleep perturbations. Furthermore, deleting VGLUT3 in the DR attenuated stress-induced sleep perturbations, especially after social defeat stress. In the DR, VGLUT3 is found in subsets of 5-HT and non-5-HT neurons. We observed that both populations are activated by acute stress, including those projecting to the ventral tegmental area. However, deleting VGLUT3 in 5-HT neurons minimally affected sleep regulation. These findings suggest that VGLUT3 expression in the DR drives stress-induced sleep perturbations, possibly involving non-5-HT DR^VGLUT3 neurons. [Display omitted] • VGLUT3 expression identifies subsets of 5-HT and non-5-HT DR neurons activated by acute stress • Selective activation of VGLUT3-expressing neurons in the DR modulates wake and REMS • Reduced VGLUT3 expression in the DR attenuates stress-induced sleep perturbations • VGLUT3 expression in 5-HT neurons exerts minimal influence on sleep Psychological stressors can induce maladaptive disruptions in sleep patterns. Henderson et al. show that neurons expressing VGLUT3 in the dorsal raphe nucleus (DR) are involved in the stress response and contribute to the circuit mechanisms mediating the effects of acute stress on sleep. [ABSTRACT FROM AUTHOR]