Learning-Induced Odor Modulation of Neuronal Activity in Auditory Cortex

Sensory cortices, even of primary regions, are not purely unisensory. Rather, cortical neurons in sensory cortex show various forms of multisensory interactions. While some multisensory interactions naturally co-occur, the combination of others will co-occur through experience. In real life, learning and experience will result in conjunction with seemingly disparate sensory information that ultimately becomes behaviorally relevant, impacting perception, cognition, and action. Here we describe a novel auditory discrimination task in mice, designed to manipulate the expectation of upcoming trials using olfactory cues. We show that, after learning, female mice display a transient period of several days during which they exploit odor-mediated expectations for making correct decisions. Using two-photon calcium imaging of single neurons in auditory cortex (ACx) during behavior, we found that the behavioral effects of odor-mediated expectations are accompanied by an odor-induced modulation of neuronal activity. Further, we find that these effects are manifested differentially, based on the response preference of individual cells. A significant portion of effects, but not all, are consistent with a predictive coding framework. Our data show that learning novel odor-sound associations evoke changes in ACx. We suggest that behaviorally relevant multisensory environments mediate contextual effects as early as ACx. Natural environments are composed of multisensory objects. It remains unclear whether and how animals learn the regularities of congruent multisensory associations and how these may impact behavior and neural activity. We tested how learned odor-sound associations affected single-neuron responses in auditory cortex. We introduce a novel auditory discrimination task for mice in which odors set different contexts of expectation to upcoming trials. We show that, although the task can be solved purely by sounds, odor-mediated expectation impacts performance. We further show that odors cause a modulation of neuronal activity in auditory cortex, which is correlated with behavior. These results suggest that learning prompts an interaction of odor and sound information as early as sensory cortex.