Direct piriform-to-auditory cortical projections shape auditory-olfactory integration

In a real-world environment, the brain must integrate information from multiple sensory modalities, including the auditory and olfactory systems. However, little is known about the neuronal circuits governing how odors influence and modulate sound processing. Here, we investigated the mechanisms underlying auditory-olfactory integration using anatomical, electrophysiological, and optogenetic approaches, focusing on the auditory cortex as a key locus for cross-modal integration. First, retrograde and anterograde viral tracing strategies revealed a direct projection from the piriform cortex to the auditory cortex. Next, using in vivo electrophysiological recordings of neuronal activity in the auditory cortex of awake mice, we found that odor stimuli modulate auditory cortical responses to sound. Finally, we used in vivo optogenetic manipulations during electrophysiology to demonstrate that olfactory modulation in auditory cortex, specifically, odor-driven enhancement of sound responses, depends on direct input from the piriform cortex. Together, our results identify a novel cortical circuit shaping olfactory modulation in the auditory cortex, shedding new light on the neuronal mechanisms underlying auditory-olfactory integration. Significance Statement All living organisms exist within multisensory environments, yet there is a lack in our understanding of how the brain integrates multisensory information. This work elucidates novel circuits governing auditory-olfactory integration in the auditory cortex. Our results shed new light on a relatively understudied area of multisensory research, promising a more robust understanding of how animals and humans perceive and interact within complex environments.