Thursday, April 3, 2025
4/3/2025
Development of Temporal Fine structure - PROJECT SUMMARY The broad goal of the proposed research program is to advance our understanding of sound localization. Even when a person has normal hearing, speech perception and learning in noisy reverberant environments may still be compromised due to persistently impaired binaural hearing capabilities. In more profound cases of deafness, bilateral cochlear implant users typically experience poor discrimination of interaural time differences (ITDs), potentially because of early deprivation. This proposal uses an avian model to advance our understanding of binaural development. We have developed this preparation to determine if/when there is a developmental window in which inputs from each ear are synchronized, in order for sensitivity to ITDs to develop. Sensitivity to binaural signals first appears in the brainstem and relies on sub-millisecond precision to detect ITDs. How such extreme precision comes about during development is not fully understood, and these birds provide a well understood model for measurement of precisely timed binaural signals. Our knowledge of this ITD circuit is detailed enough to test the following hypotheses about the physiology and development of sound localization circuits. In the broader context, understanding the mechanisms of sound localization should reveal common computational solutions to guide advances in hearing aid and cochlear implant design. The three overlapping areas to be investigated in this project are: 1. Determine if the representation of ITDs is plastic during development. Detection of ITDs depends on precise coding of delay, with current research on how ITDs change with head growth. We will use a unilateral conductive hearing loss (CHL) model, in which one ear canal is plugged around the onset of hearing, to induce experience dependent plasticity during the period of head growth. These experiments should allow us to determine if maps of ITD are modified by early experience. In Aim 1.2 we will focus on myelin plasticity as a potential mechanism for modification. 2. Address mechanisms underlying the emergence of temporal precision. If delays can be modified by altered experience, it is likely that normal ITD coding also shows developmental refinement. Delay lines encode time with sub-millisecond accuracy. To shed light on the mechanisms underlying ITD map formation, we will combine recordings of the extracellular field potential with intracellular recording from delay line axons to measure the development of ITD coding in the first 2 months posthatch. 3. The role of inhibition in the development of ITD coding. Given the importance of inhibition in regulating auditory brainstem activity, we will examine the nature of the inhibitory input to NL and cochlear nuclei. We will use the unilateral CHL model to induce experience dependent plasticity in map of ITD, and test the competing hypothesis to Aim 1.2, that changes in delay are correlated with changes in inhibition.
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