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 male or female mice, we found that odors modulate auditory cortical responses to sound. Finally, we used in vivo optogenetic manipulations during electrophysiology to demonstrate that olfactory modulation in the auditory cortex, specifically, odor-driven enhancement of sound responses, depends on direct input from the piriform cortex. Together, our results identify a novel role of piriform-to-auditory cortical circuitry in shaping olfactory modulation in the auditory cortex, shedding new light on the neuronal mechanisms underlying auditory–olfactory integration.

在现实世界的环境中，大脑必须整合来自多种感觉模式的信息，包括听觉和嗅觉系统。然而，人们对控制气味如何影响和调节声音处理的神经元回路知之甚少。在这里，我们使用解剖学、电生理学和光遗传学方法研究了听觉-嗅觉整合的潜在机制，重点是听觉皮层作为跨模态整合的关键基因座。首先，逆行和顺行病毒追踪策略揭示了从梨状皮层到听觉皮层的直接投射。接下来，使用清醒的雄性或雌性小鼠听觉皮层中神经元活动的体内电生理记录，我们发现气味会调节听觉皮层对声音的反应。最后，我们在电生理学中使用体内光遗传学操作来证明听觉皮层中的嗅觉调节，特别是气味驱动的声音反应增强，取决于梨状皮层的直接输入。总之，我们的结果确定了梨状到听觉皮层回路在塑造听觉皮层嗅觉调节中的新作用，为听觉-嗅觉整合的神经元机制提供了新的视角。