Encoding of acquired sound-sequence salience by auditory cortical offset responses

Behaviorally relevant sounds are often composed of distinct acoustic units organized into specific temporal sequences. The meaning of such sound sequences can therefore be fully recognized only when they have terminated. However, the neural mechanisms underlying the perception of sound sequences remain unclear. Here, we use two-photon calcium imaging in the auditory cortex of behaving mice to test the hypothesis that neural responses to termination of sound sequences ("Off-responses") encode their acoustic history and behavioral salience. We find that auditory cortical Off-responses encode preceding sound sequences and that learning to associate a sound sequence with a reward induces enhancement of Off-responses relative to responses during the sound sequence ("On-responses"). Furthermore, learning enhances network-level discriminability of sound sequences by Off-responses. Last, learning-induced plasticity of Off-responses but not On-responses lasts to the next day. These findings identify auditory cortical Off-responses as a key neural signature of acquired sound-sequence salience.