Motor Modulation of Auditory Processing

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DESCRIPTION (provided by applicant): Auditory sensations reflect a mixture of self-generated sounds, such as those created when we speak or play a musical instrument, and sounds arising from other sources, such as a blaring siren. Distinguishing between these two classes of stimuli is a major challenge that the auditory system must overcome to generate stable auditory percepts and facilitate auditory-guided behaviors. Evidence from a wide variety of sensory systems, including the auditory system, indicates that harnessing a copy of a motor command signal to modulate sensory processing in a movement-dependent manner facilitates this distinction. Although such motor-sensory interactions are widespread in the auditory system, motor cortical modulation of auditory cortical activity is thought to be important to higher-order auditory function necessary to communication. Moreover, dysfunction of cortical corollary discharge machinery is speculated to underlie auditory hallucinations characteristic of psychoses. Despite their postulated role in normal and disordered audition, the synaptic and circuit mechanisms underlying interactions between the motor and auditory cortices remain enigmatic. Here we propose to integrate genetic, synaptic, circuit, and behavioral methods in the mouse to map the structure and function of circuits that convey motor-related signals to the auditory cortex and to test the role of these circuits in auditory cortical processing. The propose experiments will delineate the structural and functional properties of cortical circuitry that facilitates normal auditory function during self- generated movements, including vocalization. The significance of the proposed research to the NIH mission is four-fold. First, this research can inform how the nervous system mediates normal hearing during self- generated movements; this ability is essential to speech comprehension and learning, and also is fundamental to the learning and execution of complex skills, including musical performance. Second, dysfunction of this motor to auditory interaction at the cortical level is thought to drive auditory hallucinations; a synaptic characterization of this interaction is a necessary step to understand the genesis of these pathologies and to ultimately design appropriate therapies. Third, an understanding of how motor circuits modulate hearing may provide insights into how these circuits can be manipulated either through perceptual training or direct manipulation of neural activity to facilitate auditory comprehension in the face of hearing loss. Fourth, analyzing the properties of these corollary discharge circuits in the absence of hearing, as also proposed here, can provide insights into how the brain reorganizes in response to deafness.