Phasic Activation of Dorsal Raphe Serotonergic Neurons Increases Pupil Size

• Published in: Current biology 2021-01, Vol.31 (1), p.192-197.e4
• Main Authors: Cazettes, Fanny, Reato, Davide, Morais, João P., Renart, Alfonso, Mainen, Zachary F.
• Format: Article
• Language: English
• Subjects: Animals; arousal; Arousal - physiology; behavioral states; dorsal raphe; Dorsal Raphe Nucleus - cytology; Dorsal Raphe Nucleus - physiology; Female; foraging; Lasers; Light; Male; Mice; Mice, Transgenic; Models, Animal; mouse; neuromodulation; Optogenetics; Photic Stimulation - instrumentation; pupil; Pupil - physiology; Pupil - radiation effects; Serotonergic Neurons - metabolism; serotonin; Serotonin - metabolism; Serotonin Plasma Membrane Transport Proteins - genetics; Serotonin Plasma Membrane Transport Proteins - metabolism; Uncertainty
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2020.09.090

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 regions5,9–11 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 arousal16 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. [Display omitted] •Phasic optogenetic activation of DRN 5-HT neurons increases pupil size•The effects of 5-HT neuron activation are not specific to behavioral states•The effects of 5-HT on pupil size are linked to the level of uncertainty The effects of serotonin (5-HT) on pupil size have not been investigated in detail. Cazettes et al. show that phasic optogenetic activation of 5-HT neurons causes pupil size changes in mice performing a foraging task. The 5-HT effects on pupil size are not specific to behavioral variables but appear to be linked to the task statistics.