Inverted U-shape modulation of locus coeruleus (LC) norepinephrine (NE) neurons on functional network dynamics

Motivation: Previous studies found LC-NE activity monotonically induced increases of arousal level and global functional connectivity (FC) in anesthetized mice, which contradicted to the inverted U-shaped relationship between NEnergic system and FC dynamics in our awake marmoset fMRI results. Goal(s): We aimed to uncover whether the relationship between LC-NE activity and global FC is monotonic or not. Approach: In this study, we applied awake mouse EEG-fMRI and simultaneous calcium recording and chemogenetics to explore the causal relationship between LC-NE activity and whole-brain FC dynamics along with arousal fluctuations. Results: We revealed inverted U-shaped modulation of LC-NE activity on FC dynamics along with arousal fluctuations. Impact: We provided the causal evidence of arousal modulated inverted U-shape modulation on global FC dynamics by LC-NE activities, uncovering the potential neural mechanism of arousal modulated inverted U-shape behavioral performance in humans.