Abstract
Transient variations in pupil size (PS) under constant luminance are coupled to rapid changes in arousal state,(1-3) which have been interpreted as vigilance,(4) salience,(5) or a surprise signal.(6-8) Neural control of such fluctuations presumably involves multiple brain regions(5)(,)(9-11) and neuromodulatory systems,(3)(,)(12)(,)(13) but it is often associated with phasic activity of the noradrenergic system.(9)(,)(12)(,)(14)(,)(15) Serotonin (5-HT), a neuromodulator also implicated in aspects of arousal(16) such as sleep-wake transitions,(17) motivational state regulation,(18) and signaling of unexpected events,(19) seems to affect PS,(20-24) but these effects have not been investigated in detail. Here we show that phasic 5-HT neuron stimulation causes transient PS changes. We used optogenetic activation of 5-HT neurons in the dorsal raphe nucleus (DRN) of head-fixed mice performing a foraging task. 5-HT-driven modulations of PS were maintained throughout the photostimulation period and sustained for a few seconds after the end of stimulation. We found no evidence that the increase in PS with activation of 5-HT neurons resulted from interactions of photostimulation with behavioral variables, such as locomotion or licking. Furthermore, we observed that the effect of 5-HT on PS depended on the level of environmental uncertainty, consistent with the idea that 5-HT could report a surprise signal.(19) These results advance our understanding of the neuromodulatory control of PS, revealing a tight relationship between phasic activation of 5-HT neurons and changes in PS.