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Serotonergic signaling governs C. elegans sensory response to conflicting olfactory stimuli

Srinivasan, J.; Muirhead, C. S.; Guerra, S.; Fox, B. W.; Schroeder, F. C.

2025-03-19 neuroscience
10.1101/2025.03.19.644218 bioRxiv
Show abstract

Neural circuits that consolidate sensory cues are essential for neurological functioning. Neural circuits that perform sensory integration can vary greatly because the sensory processing regions of the brain employ various neural motifs. Here, we investigate a neural circuit that mediates the response to conflicting olfactory stimuli in C. elegans. We concurrently expose animals to an aversive dispersal pheromone, osas#9, and an attractive bacterial extract. While worms usually avoid osas#9 alone, they suppress this avoidance behavior in the presence of a bacterial extract. Loss-of-function mutants and cell-specific rescues reveal that serotonergic signaling from the ADF neuron is essential for bacterial extract-induced osas#9 avoidance attenuation. The inhibitory serotonin receptor, MOD-1, which is widely expressed on interneurons and motor neurons, is required for this sensory integration, suggesting that serotonin acts in an inhibitory manner. By performing calcium imaging on the ADF neurons in synaptic signaling (unc-13) and peptidergic (unc-31) signaling mutant backgrounds, we show that the ADF neurons require input from other neurons, likely the ASK neurons, to respond to food extracts. We reveal a cue integration neural circuit in which serotonergic signaling at the sensory neuron level silences an aversive neural signal. SignificanceAnimals use sensory cues to make behavioral choices and sometimes, these cues convey opposite information. The nervous system consolidates competing sensory cues to create a coherent response to external stimuli. The neural circuits that govern this process are important, and still largely unknown. We use C. elegans, a soil-dwelling nematode, to uncover a neural circuit governing the consolidation of competing cues by concurrently exposing worms to positive and negative stimuli . We find that the neurotransmitter serotonin can suppress aversive neural signals created by negative stimuli. These results show the important neurological role that serotonin plays in modulating neural signals.

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