Auditory cortical processing of self-generated sounds - PROJECT SUMMARY Hearing is necessary for skilled acoustic behaviors like speech and music. While learning and performing behaviors like these, we listen to the sounds that our actions produce, we compare what we heard with what we expected to hear, and we detect mismatches between expectation and experience (i.e. errors) that can be used to update subsequent behaviors. The auditory cortex is critical for skilled acoustic behaviors like this, and auditory cortex cells integrate signals related to sound, behavior, expectation, and error. To understand how the auditory system works during behavior, it is imperative to learn how all of these signals are integrated within and used by hearing centers of the brain. However, it remains unknown how neural circuits integrate motor, acoustic, and goal-related signals to detect errors and guide learning. In this proposal, we will test the hypothesis that the mouse auditory cortex integrates sound and behavior-related signals during skilled acoustic behaviors, detects errors, and routes error-related signals to motor regions of the brain to adapt subsequent acoustic behaviors. To facilitate the use of lab mice for studying skilled acoustic behavior, we have developed a skilled auditory-guided forelimb behavior for mice that requires hearing. Using this paradigm, we will combine quantitative behavior with large-scale physiology, circuit perturbation, and anatomical tracing to determine how the auditory system detects acoustic errors and uses errors to guide skilled acoustic behavior. In Aim 1, we will first establish that skilled, sound-guided behaviors in mice require hearing and auditory cortex activity. We will then combine high-channel count physiology with behavior to identify populations of auditory cortex neurons that carry signals related to sound, behavior, and error. Finally, we will determine whether distinct auditory cortical error signals correlate with subsequent behavioral corrections. In Aim 2, we will first establish that motor cortex is necessary for skilled acoustic behavior. We will then combine electrophysiology with optogenetic “photo-tagging” to determine whether auditory cortex error signals are concentrated in neurons that project to the motor cortex. Finally, we will use optogenetic silencing to test whether auditory cortical neurons that project to motor cortex are necessary for driving behavioral changes. In Aim 3, we will first make physiological recordings from motor cortex to identify preparatory activity patterns that encode upcoming behaviors. We will then make simultaneous recordings from auditory and motor cortex to determine whether transient auditory error signals correlate with changes in motor planning activity on a trial-by-trial basis. Finally, we will ask whether auditory cortical error signals are necessary for updating motor cortex preparatory activity following behavioral errors.
