Visual attention is linked to temporally structured noradrenaline release in the medial prefrontal cortex

Abstract Visual attention enables filtering of irrelevant stimuli and focus on information that is most pertinent to survival. While the locus coeruleus-noradrenaline (LC-NA) system is recognized as crucial in this process, the role of temporally structured NA signaling in visual attentional performance remains unsettled. Here, by using the genetically encoded NA sensor GRAB NE2h together with fiber photometry in mice, we identify sub-second NA release signatures in the medial prefrontal cortex (mPFC) that correlate with visual attention accuracy in the rodent Continuous Performance Test (rCPT). The dual-peak release signatures were time-locked to correct, rewarded responses, preceded by a ramp-up after stimulus presentation and followed by a decline at reward collection. No such signatures accompanied misses, correct rejections and mistakes. Similar, albeit less pronounced, patterns were observed in the lateral hypothalamus (LH). Activation of the Gq-coupled DREADD (Designer Receptors Exclusively Activated by Designer Drugs) hM3DGq expressed in LC neurons dose-dependently increased tonic NA levels in both mPFC and LH, while simultaneously distorting phasic NA signatures and impairing rCPT performance without affecting locomotor activity. Summarized our data suggest that NA enhances alertness to reward-associated stimuli through precise, dynamic release patterns underscoring its role in modulating attentional performance beyond tonic signaling.