Dissecting the functional organization of the C. elegans serotonergic system at whole-brain scale

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 in-creases 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.

Automated summary

This study reveals how serotonin release in C. elegans alters brain-wide activity to induce foraging behaviors and identifies the core serotonin receptors involved in slow locomotion and feeding modulation. Whole-brain imaging shows widespread serotonin-associated brain dynamics and mapping of serotonin receptor expression in the connectome helps predict neurons' serotonin-associated activity. These findings provide insights into how serotonin acts across the connectome to modulate brain-wide activity and behavior.