Function of orexin-1 receptor signaling in the olfactory tubercle in odor-guided attraction and aversion

While olfactory behaviors are influenced by neuromodulatory signals, the underlying mechanism remains unknown. The olfactory tubercle (OT), a component of the olfactory cortex and ventral striatum, consists of anteromedial (am) and lateral (l) domains regulating odor-guided attractive and aversive behaviors, respectively, in which the amOT highly expresses various receptors for feeding-regulated neuromodulators. Here we show functions of appetite-stimulating orexin-1 receptor (OxR1) signaling in the amOT. When odor-food reward associated mice underwent OxR1 antagonist injection in the amOT, their odor-attractive behavior was suppressed and odor-aversive behavior was conversely induced. Although odor-attractive mice showed activation of attraction-promoting dopamine receptor type 1-expressing D1 cells in the amOT, the antagonist injection increased activation of aversion-promoting D2 cells in the amOT and D1 cells in the lOT. The results highlight the amOT as the crucial structure integrating OxR1 signaling and odor information, thereby controlling metabolic status-dependent olfactory behavior through the cell type- and domain-specific activation. Local manipulation of orexin signaling reveals that the anteromedial domain of the OT is the crucial region that integrates odor information and metabolic signals and directs appropriate odor-guided feeding behavior according to metabolic status.