Adaptive co-transmission shapes sensory encoding and behavior

ABSTRACT Co-transmission expands the chemical repertoire of neurons, but whether coexisting neurotransmitters can be independently organized and remodeled by experience to control distinct aspects of behavior remains unclear. Here, we address this question in the AFD thermosensory neuron of Caenorhabditis elegans , which directs navigation toward a learned temperature preference. We find that glutamatergic and cholinergic vesicular transporters coexist within individual presynaptic boutons but differ in axonal trafficking, subsynaptic organization, and dependence on presynaptic machinery. Sensory experience differentially regulates the two systems: animals trained to prefer higher temperatures exhibit increased VGLUT/EAT-4 abundance, whereas those trained to prefer lower temperatures exhibit increased VAChT/UNC-17 abundance. The two transmitters also make distinct, context-dependent contributions to goal-directed navigation. Glutamatergic transmission promotes movement toward the learned thermal preference, whereas cholinergic transmission restrains continued migration beyond it. Analysis of locomotor trajectories further reveals that the two transmitters differentially regulate reorientation decisions across regions of the thermal gradient. Together, these findings identify adaptive co-transmission , a form of synaptic plasticity in which coexisting neurotransmitter systems are differentially organized and regulated by experience, and make distinct, context-dependent contributions to behavior.