BRAIN-WIDE EFFECTS OF BIDIRECTIONAL OPTOGENETIC MODULATION OF NORADRENALINE

Brain states profoundly influence perception and behavior, and the locus coeruleus–noradrenaline (LC–NA) system is a key regulator of these dynamics. While pupil diameter is widely used as a proxy for LC–NA activity, the direct brain-wide consequences of bidirectional NA modulation are incompletely characterized. Here, we combined functional ultrasound imaging (fUSi) with optogenetic activation (ChR2) and inhibition (ACR2) of the LC in mice to causally probe NA-dependent large-scale dynamics. LC activation induced rapid and robust pupil dilation accompanied by global vasoconstriction. In contrast, LC inhibition produced slower pupil constriction followed by widespread vasodilation across the brain, demonstrating a clear bidirectional control of large-scale hemodynamic activity by noradrenergic tone. To assess whether LC–NA activity is influential on natural arousal dynamics, we analyzed spontaneous and sensory-evoked arousal bouts during LC manipulation. Despite strong global hemodynamic shifts induced by optogenetic tuning, the characteristic spatiotemporal structure of natural arousal responses remained largely preserved.
Together, these findings indicate that LC–NA powerfully modulates baseline brain-wide vascular dynamics, yet does not directly generate or abolish the canonical arousal wave. This suggests that natural arousal emerges from a broader network-level orchestration beyond LC tone alone.