Activity-Dependent Influences on Auditory Circuits

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DESCRIPTION (provided by applicant): The overall goal of the proposed research is to better understand the impact of degraded auditory experience on brain function, the mechanisms by which these changes occur, and how such knowledge can contribute to the development of effective remediation strategies. Degraded hearing in the form of conductive hearing loss (CHL) such as otitis media with effusion is the most commonly diagnosed illness among children in the United States and has been repeatedly associated with deficits in auditory perceptual processes that persist for years after the conductive loss has been resolved. To better understand the mechanisms underlying these enduring processing deficits, we have utilized a technique for reversible CHL that permits precise control over the timing and bilateral expression of developmental hearing loss. The proposed experiments will relate a history of CHL to plasticity of single neuron response properties and their coordinated arrangement into functional maps. Initial experiments will vary the age of CHL onset to delineate the sensitive period regulation of binaural processing in the inferior colliculus, medial geniculate body and primary auditory cortex. Continuing studies will compare the effects of unilateral versus bilateral CHL on the functional organization of midbrain and forebrain nuclei and identify the aspects of plasticity that endure versus those that fade away once normal hearing has been restored. A second line of research will provide a comprehensive assessment of experience-dependent influences on monaural and binaural stimulus selectivity in the auditory cortex. These studies will document plasticity in the encoding of sound spectra, signal-to-noise ratio, temporal envelope variations as well as interaural level and time differences at the level of the single neuron in the awake animal. By documenting how critical "real-world" variables such as the timing of CHL, the bilateral pattern of CHL and the length of CHL-free hearing impact the developing central auditory system, these studies further inform health care practitioners about the costs and benefits associated with various intervention strategies for childhood CHL. These experiments will further our understanding of how experience shapes brain function and behavior. The proposed work will examine the instructive role of experience in the formation of brain circuits that mediate binaural hearing. By combining a method for reversible conductive hearing loss with techniques to characterize plasticity at the level of single neurons and representational maps in auditory midbrain and forebrain nuclei, the proposed studies introduce a promising approach to address basic research questions regarding experience-dependent plasticity and translational questions related to the pathophysiology of childhood hearing loss.