Circuit mechanisms underlying temporal processing in auditory cortex

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Project Summary Over half of those over 65 years old have age-related hearing loss, and the primary communication challenge reported by older adults is difficulty understanding speech in noisy conditions, such as a crowded restaurant. Age-related speech processing deficits can occur even with completely normal audiometric hearing, and are instead associated with temporal processing deficits in central structures such as auditory cortex. The mechanisms underlying temporal processing in auditory cortex are not well understood. Our broad goal is to elucidate these mechanisms. We will use a well-established measure of temporal processing in both humans and animals: the ability to detect a brief gap in background noise. The circuitry underlying gap detection in cortex remains unknown. In Aim 1 we seek to elucidate this circuitry by combining neuronal recording and optogenetics in awake mice performing a gap detection task. In Aim 2 we seek to understand how gap detection is enhanced when fear conditioning confers emotional significance to the gap. We propose to use fear potentiation of gap detection in mice as a model for how associative learning in auditory cortex assigns meaning to temporally structured sounds such as speech. We will use neuronal recording and optogenetics before, during, and after fear conditioning to determine the cortical circuit mechanisms underlying the associative learning of temporal structure. In both aims, our hypotheses are expressed as a candidate neural circuit model which makes specific predictions. In each Aim we will test these predictions, using the results to refine the model. Our broad goal is to understand which cortical neurons and circuits are necessary for gap detection and fear potentiation of gap detection, and how the dynamics of these circuits mediate these processes. Achieving this goal will provide fundamental new insights into the mechanisms underlying temporal processing, and how alterations of these mechanisms could contribute to age-related deficits in speech comprehension.