Cortical areas function as adaptive sensory processors, subject to robust top-down modulations of high-order brain areas, such as arousal, attention, and perceptual learning. A large body of evidence shows that the anterior cingulate cortex (ACC) could be a cognitive center that integrates and regulates the activities of the neurons in the whole brain through a direct or indirect pathway. However, the diverse functions of ACC's different axon projections to other areas remain poorly understood.

In this work, we demonstrated for the first time that the anterior part of the ACC of mice encoded air-puff information from the environment and sent such information to the auditory cortex (ACx). Direct activation of ACC projections in the ACx potentiated auditory responses within a time window and enhanced mice’s auditory-based flight running in our behavioral paradigm.

Following this discovery, we proved that the anterior ACC promoted a long-term change in auditory responses in the ACx through the lateral rhinal cortex (lRCx). After high-frequency laser activation in aACC, we found that the ACx's auditory-evoked potential (AEP) formed long-term potentiation (LTP). Anterograde and retrograde tracing experiments suggested that aACC had two groups of neurons that separately projected to ACx and lateral RCx. The inhibition of lRCx blocked the ACC-promoted AEP-LTP formation in ACx.

Finally, we found that the lateral RCx neurons receiving projects from aACC had direct projections in the ACx. High-frequency activating aACC projections in lRCx can also lead to ACx AEP- LTP. In the behavior context, the ACC-> lRCx projections activation facilitated mice sound-evoked flight responses even in an hour.

In summary, the ACC's anterior part directly enhanced auditory cortical responses in air-puffing-facilitated flight behavior. It also promoted a long-term potentiation of auditory responses in the ACx through projections in the lRCx. It had the potential to modulate the ACx in direct and indirect strategies, which may contribute to a higher level of cortical sensory perception and cognition. This study may help further elucidate the ACC top-down modulation of ACx processing.