Project Summary Learning is a fundamental function of the brain: sensory representations must be flexible to adjust to changes in environmental demands and experience, thus allowing us to adapt to the world around us. Understanding the mechanisms of learning are important not only for normal function of the brain but also in disease, for example, after unilateral hearing loss. One important but often overlooked principle of learning is the importance of feedback from other brain areas. In this grant I propose to investigate the function of corticofugal feedback, from auditory cortex (ACx) to inferior colliculus (IC), in sound localization learning after unilateral hearing loss. I will test (1) the hypothesis that the function of cortico-collicular feedback is to provide information about the current sensory conditions using optogenetics and behavior; and (2) the hypothesis that acetylcholine (ACh) release in ACx modulates activity in IC during learning, using fiber photometry to record ACh release dynamics in ACx and neural activity in IC simultaneously. In the independent phase, I will test (3) the hypothesis that burst activity in feedback from ACx to IC contains an error signal which directs plasticity in IC and leads to behavioral adaptation to the new listening environment using electrophysiology and opto-tagging in ACx and IC. Understanding the mechanisms by which the brain compensates for changes in sensory input can provide information about how to best develop treatments, such as hearing and other sensory aids, or perceptual training for patients who experience such losses, thus improving their ability to communicate and quality of life.

Project Narrative The goal of the proposed research is to identify the circuit-level mechanisms in the auditory cortex and inferior colliculus that underlie learning after unilateral hearing loss. Patients with hearing deficits or age-related hearing loss exhibit disproportionate difficulty hearing especially when several sound sources are present. Understanding the mechanisms by which the brain compensates for hearing loss can provide information about how to best develop treatments, such as hearing aids (or other sensory aids), or perceptual training for patients who experience such losses, thus improving their ability to communicate and quality of life.