Calcium levels in ASER neurons determine behavioral valence by engaging distinct neuronal circuits in C. elegans

The valence of stimuli is shaped by various factors, including environmental cues, internal states, genetic variability, and past experience. However, the mechanisms behind this flexibility remain elusive. In the nematode C. elegans, we found that ethanol, an olfactory stimulus, can elicit opposite chemotaxis responses - attraction vs. aversion - depending on NaCl concentration, demonstrating the role of environmental factors in altering valence. Remarkably, a single chemosensory neuron, ASER, orchestrate this bidirectional ethanol chemotaxis by integrating information from both stimuli - ethanol and NaCl - into its neuronal activity dynamics. Specifically, different calcium dynamics in the ASER neuron differentially activate the signaling molecule CMK-1, thereby engaging different downstream interneurons and leading to opposite chemotaxis directions. Consistently, optogenetic manipulations of the ASER neuron reverse the chemotaxis directions, by altering its calcium dynamics. Our findings reveal a mechanism by which a single neuron integrates multisensory inputs to determine context-dependent behavioral valence, contributing to our current understanding of valence encoding.