The nucleus of the lateral olfactory tract is required for learning odor-guided food avoidance

Abstract Foraging animals must continually evaluate whether potential food sources are safe to consume. Such decisions rely on both innate preferences and learned associations formed through prior experience. Consumption of a food followed by malaise or sickness leads to avoidance of that food, reflecting learned associations between sensory cues that identify a food and its negative post-ingestive consequences. Although this form of learning has been studied extensively using taste cues, taste signals arise only after oral contact, at which point exposure to potential toxins has already occurred. Olfactory cues, in contrast, provide information about potential food sources prior to consumption, yet how odors acquire aversive value remains unclear. Here, using targeted chemogenetic perturbations, we identify the nucleus of the lateral olfactory tract (NLOT), which has direct bidirectional connectivity to olfactory regions and the basolateral amygdala, as a critical circuit element for odor-aversion learning. We find that the NLOT is required for conditioned odor aversion but is dispensable for other odor-guided behaviors and for fear conditioning driven by a non-olfactory cue. Our findings identify a selective role for the NLOT in linking olfactory cues to learned aversive outcomes, that supports odor-guided behavioral decisions. Significance statement Animals rely on smell to evaluate food safety before consuming it, yet the brain circuits that link odor cues to learned aversive outcomes remain poorly understood. Here we identify the nucleus of the lateral olfactory tract (NLOT), a largely unstudied region at the interface between olfactory and limbic circuits, as a critical and selective node for conditioned odor aversion learning. Chemogenetic perturbations of the NLOT disrupted both the acquisition and expression of odor-malaise associations, while leaving odor detection, odor discrimination, and non-olfactory fear learning intact — revealing a previously unrecognized specialization within olfactory-amygdala circuits that supports odor-guided decisions about food safety.