Mitochondrial dynamics in the rat dorsal raphe nucleus underlie sleep pressure and sleep structure regulation

Abstract

Abstract Circadian rhythm and sleep homeostasis processes regulate sleep and wakefulness in mammals, which are highly interconnected with serotonergic circuits that originate in the dorsal raphe nucleus (DRN). Higher serotonin levels during wakefulness may exert “sleep pressure” and lead to sleep onset, but the mechanisms are unclear. Proteomics analysis indicated that mitochondria are key mediators. The present study found that an increase in mitochondrial fission and oxidative phosphorylation/electron transfer capacity were coupled with a reduction of sleep pressure in rats. When mitochondrial fission was moderately inhibited, wake-promoting and non-rapid-eye-movement sleep-enhancing effects were found to result from the activation of serotonergic function. These findings indicate that sleep homeostasis is highly integrated with the mitochondrial dynamic process in the rat DRN. Our findings support a conceptual framework by which mitochondria and energy metabolism in the rat DRN are introduced into the serotonergic modulation of sleep-wake states and provide evidence of sleep evolution from an energy-balance perspective.