Serotonin influences many aspects of animal behavior. But how serotonin acts on its diverse receptors across the brain to modulate global activity and behavior is unknown. Here, we examine how serotonin release in C. elegans alters brain-wide activity to induce foraging behaviors, like slow locomotion and increased feeding. Comprehensive genetic analyses identify three core serotonin receptors (MOD-1, SER-4, and LGC-50) that induce slow locomotion upon serotonin release and others (SER-1, SER-5, and SER-7) that interact with them to modulate this behavior. SER-4 induces behavioral responses to sudden increases in serotonin release, whereas MOD-1 induces responses to persistent release. Whole-brain imaging reveals widespread serotonin-associated brain dynamics, spanning many behavioral networks. We map all sites of serotonin receptor expression in the connectome, which, together with synaptic connectivity, helps predict which neurons show serotonin-associated activity. These results reveal how serotonin acts at defined sites across a connectome to modulate brain-wide activity and behavior.

血清素影响动物行为的许多方面。但血清素如何作用于大脑中的不同受体来调节整体活动和行为尚不清楚。在这里，我们研究了秀丽隐杆线虫中血清素的释放如何改变全脑活动以诱导觅食行为，例如缓慢运动和增加进食。全面的遗传分析确定了三种核心血清素受体（MOD-1、SER-4 和 LGC-50），它们在血清素释放时诱导缓慢运动，以及与它们相互作用的其他受体（SER-1、SER-5 和 SER-7）调节这种行为。 SER-4 诱导对血清素释放突然增加的行为反应，而 MOD-1 诱导对持续释放的反应。全脑成像揭示了广泛的与血清素相关的大脑动力学，跨越许多行为网络。我们绘制了连接组中血清素受体表达的所有位点，这与突触连接一起有助于预测哪些神经元表现出血清素相关活性。这些结果揭示了血清素如何在连接组的特定位点发挥作用，从而调节全脑活动和行为。