CIRCUIT MECHANISMS OF SOUND PROCESSING AND DETECTION IN THE AUDITORY PATHWAY Auditory perception relies on predicting statistics of incoming signals, be it identifying the speech of a conversation partner in a crowded room or recognizing the sound of a bubbling brook in a forest. The human brain detects statistical regularities in sounds as a fundamental aspect of prediction, evidenced by reduced responses to repeated sound patterns and enhanced responses to unexpected sounds. Multiple studies demonstrate that the neuronal responses to regular signals are reduced through adaptation, which can contribute to prediction. However, adaptation alone is not sufficient to account for prediction and studies at cellular and neuronal population level in animals thus far lend onto partial support to existing theories of predictive coding. As such, the circuit level mechanisms for the prediction of statistical regularities beyond tone frequency in sounds, and their role in behavior, remain unknown. Our goal is to close this gap in knowledge and to determine the circuits that predict signals and detect statistical regularity and its violation in auditory behavior. To identify feedforward and feedback components of prediction of statistical regularities in sounds in the auditory system, we combine optogenetic selective perturbation and large-scale imaging and electrophysiology with behavioral methods in awake mice. First, we test whether and how excitatory-inhibitory interactions within the auditory cortex (AC) establish predictive code for sound patterns, detect statistical regularities, and contribute to enhanced responses for unexpected sounds. Second, we test whether and how detection of statistical regularities at the neuronal level contributes to behavioral detection of change in sound regularity. Third, we test whether and how feedback from higher cortical areas provides information about regularity and violation. Our results will identify the neuronal circuits for encoding statistical regularity and its violation in sound and establish their role in auditory behavior.
The goal of the proposed research is to identify the circuit-level mechanisms in the auditory cortex and anterior cingulate cortex that underlie auditory prediction and to test the way these mechanisms contribute to behavioral detection of regularity in sounds and its violation. This is achieved by using a combination of electrophysiological, optogenetic and behavioral approaches in the mouse system. Patients with hearing deficits, age-related hearing loss and communication deficits, exhibit disproportionate difficulty hearing when several sound sources are present. Identifying the function of specific neuronal circuits in the auditory pathway and their relation to predictive coding, which has been implicated in auditory source segregation, is a prerequisite for development of new and improvement of existing therapies for these large groups of patients.
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