Transient variations in pupil size (PS) under constant luminance are coupled to rapid changes in arousal state,1, 2, 3 which have been interpreted as vigilance,⁴ salience,⁵ or a surprise signal.6, 7, 8 Neural control of such fluctuations presumably involves multiple brain regions^5,9, 10, 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, 21, 22, 23, 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.

恒定亮度下瞳孔大小 (PS) 的瞬态变化与唤醒状态 1、2、3 的快速变化相关联，这些变化已被解释为警惕、⁴突出、⁵或意外信号。 6、7、8 此类的神经控制波动大概涉及多个大脑区域^{5 、} 9 、 10 、 11 和神经调节系统^{3 、12 、13 ，}但它通常与去甲肾上腺素能系统的阶段性活动有关。^{9 , 12 , 14 , 15}血清素 (5-HT)，一种神经调节剂，也涉及唤醒的各个方面^16，例如睡眠-觉醒转换，¹⁷动机状态调节，¹⁸和突发事件信号，¹⁹似乎影响 PS,20, 21, 22, 23, 24 但这些影响尚未详细研究。在这里，我们表明阶段性 5-HT 神经元刺激会导致瞬态 PS 变化。我们在执行觅食任务的头部固定小鼠的中缝背核 (DRN) 中使用了 5-HT 神经元的光遗传学激活。5-HT 驱动的 PS 调制在整个光刺激期间保持不变，并在刺激结束后持续几秒钟。我们没有发现任何证据表明 5-HT 神经元激活导致 PS 增加是由光刺激与行为变量（如运动或舔）的相互作用引起的。此外，我们观察到 5-HT 对 PS 的影响取决于环境不确定性的水平，这与 5-HT 可以报告意外信号的想法一致。¹⁹ 这些结果加深了我们对 PS 的神经调节控制的理解，揭示了 5-HT 神经元的阶段性激活与 PS 变化之间的密切关系。