Glia-released serotonin drives nose touch responses in Caenorhabditis elegans

Touch is essential for survival, guiding interactions with the environment and forming the basis of social and emotional connection. While touch perception is mediated by mechanoreceptors composed of neurons and glia, the role of glia in mechanosensation remains poorly understood. Here, we uncover a previously unrecognized function for glia-derived serotonin in regulating touch sensitivity in Caenorhabditis elegans . Using in vivo Ca 2+ and serotonin imaging, fluorescence microscopy, and behavioral assays, we show that amphid sheath (AMsh) glia release serotonin via dense core vesicles. This serotonin activates the neuronal receptor SER-5 to enable ASH neuron responses, while simultaneously engaging glial MOD-1 autoreceptors to provide feedback control. We further identify a concentration-dependent mechanism that fine-tunes sensory sensitivity through cAMP- and Ca 2+ -dependent pathways. Together with prior evidence of glial GABA release, our findings establish glia as active regulators of touch, balancing excitation and inhibition to maintain mechanosensory function.