Activation of locus coeruleus noradrenergic neurons rapidly drives homeostatic sleep pressure

Authors: Daniel Silverman, Changwan Chen, Shuang Chang, Lillie Bui, Yufan Zhang, Rishi Raghavan, Anna Jiang, April Le, Dana Darmohray, Jiao Sima, Xinlu Ding, Bing Li, Chenyan Ma, Yang Dan

Published: 2025-01-17

DOI: 10.1126/sciadv.adq0651

Source: Full article


Abstract

Homeostatic sleep regulation is essential for optimizing the amount and timing of sleep for its revitalizing function, but the mechanism underlying sleep homeostasis remains poorly understood. Here, we show that optogenetic activation of locus coeruleus (LC) noradrenergic neurons immediately increased sleep propensity following a transient wakefulness, contrasting with many other arousal-promoting neurons whose activation induces sustained wakefulness. Fiber photometry showed that repeated optogenetic or sensory stimulation caused a rapid reduction of calcium activity in LC neurons and steep declines in noradrenaline/norepinephrine (NE) release in both the LC and medial prefrontal cortex (mPFC). Knockdown of α