Molecular and Physiological Diversity of MSO Neurons and the Influence of Auditory Experience

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Project Summary The Medial Superior Olive (MSO) is a mammalian brainstem nucleus that computes cues used for azimuthal sound localization (interaural time differences, ITDs). Functionally, sound localization has been theorized to be a necessary component not just for the simple acquisition of spatial information, but also for higher order processing, such as language acquisition. 13% of people in the United States have some degree of hearing loss in both ears1, but we do not fully understand how these deficits impact the ability to perform basic computations, such as bilateral integration. Therefore, this work seeks to address specifically how models of hearing loss may impact neural diversity. Based on recent findings in our lab, the MSO contains a previously undescribed diverse population of repetitive firing neurons that are morphologically indistinguishable from phasic neuron counterparts, but respond to similar inputs. The membrane and response properties of these neurons are consistent with the time course of slower components of sounds, such as envelopes. This evidence suggests that the diversity of MSO response patterns may reflect the ability of the nucleus to encode a broader array of sound features than previously thought. Within this context, we question whether situations of hearing loss may restrict diversity of response properties, and thus irreparably effect the ability of mammals to respond to both fast and slow spatial cues. To test this hypothesize, we plan to use a combination of electrophysiology and immunohistochemistry to measure response patterns of MSO neurons in a conductive hearing loss model and a model of decorrelated information, lacking spatial cues. We predict that if repetitive firing neurons of the MSO are not present in the two experimental models, then normally patterned auditory stimuli are likely necessary for the development of these response types. Secondly, we hypothesize that the diversity of response types stems from a mechanistic alteration of spike generation in MSO neurons. We predict that in models of hearing loss, auditory features will no longer fine-tune the expression of voltage-gated sodium channels to generate a diverse set of responses. We will test this by using antibody labeling for specific subunits of sodium channels and pulling nucleated patches to isolate and measure somatic sodium currents. Together, these results will push our understanding of how hearing loss affects diverse populations of neurons, while adding to our much-needed understanding of how intrinsic neuron properties are shaped by auditory activity.