Project Summary Neurons throughout the auditory system are remarkably plastic, allowing auditory circuits to flexibly adapt to changing task demands and context. Flexible auditory behavior is the result of a dynamic interaction between several auditory regions including upstream and downstream areas. The auditory cortex (AC) is modulated by many behavioral factors including expectation, enagagement, and reward supporting the view that it is a hub for perception. However, AC does not operate in isolation receiving direct top-down inputs from frontal-motor cortex (M2) and bottom-up inputs from auditory thalamus (MGB) forming a central auditory axis important for auditory perception and behavior. The canonical view of auditory circuits has exclusively focused on the role of classically responsive neurons. Thus, non-classically responsive neurons with highly variable trial-to-trial firing patterns have typically been excluded from analysis despite being widely reported for decades. Thus, the mechanisms by which non-classically responsive neurons contribute to auditory processing, perception, and behavior is unclear. The goal of this proposal is to directly investigate how local circuits in AC comprised of diverse ensembles interact with downstream and upstream auditory brain regions to flexibly gate auditory behavior. We will take an unbiased, inclusive approach by considering the entire spectrum of classically to non-classically responsive neurons, to auditory perception and learning. We will record spiking and synaptic responses from adult mouse AC (Aim1), record simultaneously from AC and an auditory domain of frontal-motor cortex (M2; Aim 2), and record spiking responses from auditory thalamus (vMGB; Aim 3) during learning and perform optogenetic experiments to reveal synaptic mechanisms and network dynamics involved in perceptual learning. These experiments will provide unique insight into the neural basis of flexible auditory behaviors, and help identity novel therapeutic targets for improving hearing disorders.

Project Narrative The auditory system is remarkably plastic and can flexibly response to acoustic cues depending on task demands and context allowing for many auditory behaviors such as communication, language acquisition, and learning. This proposal aims to investigate the neural basis of flexible auditory learning using in vivo electrophysiology, behavior, and optogenetics to understand how the auditory system flexibly gates the behavioral relevance of sounds in dynamic environments. The results from the proposed experiments will provide critical insights into improved diagnosis and treatment of hearing deficits caused by disease or injury and will inform targeted therapies for central auditory processing disorders.