Molecular and cellular modulators for multisensory integration in C. elegans

In the natural environment, animals often encounter multiple sensory cues that are simultaneously present. The nervous system integrates the relevant sensory information to generate behavioral responses that have adaptive values. However, the neuronal basis and the modulators that regulate integrated behavioral response to multiple sensory cues are not well defined. Here, we address this question using a behavioral decision in C. elegans when the animal is presented with an attractive food source together with a repulsive odorant. We identify specific sensory neurons, interneurons and neuromodulators that orchestrate the decision-making process, suggesting that various states and contexts may modulate the multisensory integration. Among these modulators, we characterize a new function of a conserved TGF-β pathway that regulates the integrated decision by inhibiting the signaling from a set of central neurons. Interestingly, we find that a common set of modulators, including the TGF-β pathway, regulate the integrated response to the pairing of different foods and repellents. Together, our results provide mechanistic insights into the modulatory signals regulating multisensory integration.