Mechanism of Auditory Cortex Development and Role of NMDA Receptors

The auditory cortex (AC) which plays a crucial role in processing complex sounds undergoes significant developmental changes as a result of postnatal experience. Early auditory experience can have a profound and potentially long lasting effect on the function and structure of the AC, and influence the hearing perception and language ability. Previous studies suggest that continuous exposure to moderate-level background noise without any spectral or temporal structure during the critical period delays the establishment of the tonotopic map of the AC and impairs frequency selectivity, creating AC developmental delay (ACDD). The goal of this proposal is to study the mechanism of AC development and noise induced ACDD, and to reveal the role of NMDA receptors in AC development and ACDD. To accomplish this goal, I will (1) use chronically implanted electrodes to monitor the response properties of neurons in AC during normal development and ACDD, (2) use pre-pulse inhibition (PPI) of the acoustic startle reflex to assess temporal resolution and frequency discrimination during normal development and ACDD, and (3) evaluate the change in NMDA receptor expression by measuring mRNA and protein levels during normal development and ACDD. Three specific aims will be addressed: (1) what functional changes occuring in AC neuron during the normal development and ACDD? (2) How does the temporal resolution and frequency discrimination change during the normal development and in ACDD? (3) what role do NMDA receptors play in AC development and ACDD? The behavioral experiments outlined in this proposal will be the first to determine if there are any perceptual deficits associated with the ACDD. The research will also be the first to evaluate the role of NMDA receptors in normal and abnormal AC development. The result of these studies may lead to new insights into pharmacologic therapies for improving auditory memory and learning deficits in children, aphasia patients and cochlear implant users.