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- 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- 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. Author summary The present study characterizes the modulation of a behavioral decision in C. elegans when the worm is presented with a food lawn that is paired with a repulsive smell. We show that multiple specific sensory neurons and interneurons play roles in making the decision. We also identify several modulatory molecules that are essential for the integrated decision when the animal faces a choice between the cues of opposing valence. We further show that many of these factors, which often represent different states and contexts, are common for behavioral decisions that integrate sensory information from different types of foods and repellents. Overall, our results reveal the molecular and cellular basis for integration of simultaneously present attractive and repulsive cues to fine-tune decision-making.