PROJECT SUMMARY The auditory cortical suppression of self-generated sounds – sounds that are the predictable consequence of movements – is thought to be critical for the detection of externally generated sounds during movement. Supporting human evidence for this hypothesis is the absence of self-generated sound suppression in Schizophrenia patients who experience auditory hallucinations and attribute an external source to internal percepts of sound. The projections from secondary motor cortex (M2) to primary auditory cortex (A1) modulate auditory activity during movement and are capable of suppressing tone evoked responses via excitatory drive onto A1 inhibitory interneurons. This anatomical and functional evidence points to a putative role of M2 in the experience-dependent, frequency-specific suppression of self-generated sounds. However, little is known about the activity of M2 during sound-generating movements, how an association between action and sensory outcome is learned, and how this circuitry adapts to changing environments. This adaptation – the ability to re-learn the acoustic consequence of a movement – is critical for behaving in a changing world. This proposal will investigate the activity of mouse M2 in vivo during a sound-generating lever push movement, specifically what information M2 sends to A1 and how that information changes in parallel to changes in the acoustic consequence of the movement. Aim 1 will use optical and electrophysiological techniques to compare the activity of auditory and non-auditory projecting subpopulations in M2 during movement that creates a learned and expected sound. Aim 2, with a similar preparation, will then assess how these subpopulations respond when an unexpected sound is generated by the same movement. Finally, Aim 3 will use chronic calcium imaging to monitor how responses of the M2 subpopulations develop across the learned association between sound and movement, and how the activity and/or active population identity might change when the same movement permanently produces a new sound, and the auditory-motor association is re-learned. The predictions from these experiments are that auditory-projecting M2 populations represent the expected self-generated sound and alter their activity in response to re-learning the auditory consequence of movement. Together, this work will describe information flow from motor to auditory cortex in changing acoustic environments, which is necessary for the understanding how the auditory-motor system functions, and so is dysfunctions, in the processing of self-generated sounds.

PROJECT NARRATIVE Communication between auditory and motor cortex and the integration of these modalities of information are important for processing sounds generated by and during movement. Dysfunction of the auditory-motor network is thought to underlie auditory hallucinations seen in patients with schizophrenia, because of their deficient ability to differentiate whether a sound was self or externally generated. By describing the normal information flow between motor and auditory cortex, this project may reveal functions of the circuitry that are susceptible to disruption in psychiatric disease.