The anterior cingulate cortex modulates pupil-linked arousal.

Subcortical structures like the locus coeruleus (LC) are well known to regulate pupil-linked autonomic arousal, while the role of cortical circuits in this process remains largely unclear. We designed a closed-loop optogenetic system to inactivate the anterior cingulate cortex (ACC) in real time during pupil dilations. ACC inactivation decreased the magnitude of spontaneous pupil events. In parallel, ACC population activity scaled with the magnitude of spontaneously occurring pupil dilations. In addition to modulating spontaneous arousal, ACC responses to salient sensory stimuli scaled with the size of evoked pupil dilations and ACC inactivation suppressed saliency-linked pupil events. Last, we show that LC norepinephrine neurons signal arousal faster than the ACC. However, unlike the ACC, LC responses did not scale with the magnitude of pupil dilations. Collectively, our experiments identify the ACC as a key cortical site for sustaining momentary increases in pupil-linked arousal.