Roles of Parvalbumin-Expressing Interneurons in Physiological Changes to Primary Auditory Cortex After Hearing Loss and Blast Exposure

Abstract

Hearing loss affects approximately 1 in 8 Americans and has a significant impact on quality of life, often leading to tinnitus and central auditory processing disorder. Hearing loss causes a cascade of changes to the auditory processing pathway, starting with death of hair cells in the inner ear and ultimately causing a series of physiological changes in primary auditory cortex (AI). Blast exposure commonly affects veterans and can lead to hearing loss as well as Traumatic Brain Injury (TBI), which damages the soft tissue and vasculature of the central nervous system and can independently cause central auditory processing disorder. The distinct effects of hearing loss and TBI on auditory processing remain poorly understood. Further research is needed to identify the role of AI in auditory processing deficits after hearing loss and/or TBI, as well as to identify specific cellular mechanisms to serve as targets for potential therapeutic approaches. First, I identify changes to the primary auditory cortex of rats following blast exposure with associated hearing loss. This includes distortions in the normal tonotopic frequency map in the form of random, frequency specific expansions. Additionally, there are associated changes to the hearing threshold and bandwidth of frequency tuning at individual cortical recording sites. These changes outline broad physiological deficits in auditory processing in primary auditory cortex after blast exposure. Next, I show that blast exposure alone can impair temporal processing in AI, but concurrent hearing loss dramatically exacerbates these impairments. I dissociate the effects of blast exposure and hearing loss by protecting either one or both ears from hearing loss during blast exposure. While blast exposure without hearing loss causes deficits in temporal processing which could lead to central auditory processing disorder, blast exposure with associated hearing loss causes more numerous and severe deficits. Specifically, only blast exposure with concurrent hearing loss reduces the expression of the Parvalbumin protein in AI and causes deficits in gap detection behavior, which is used as a test for potential tinnitus. Finally, I show that hearing loss alone causes a set of changes to Parvalbumin-expressing inhibitory interneurons (PV neurons) in AI. This includes a reduction of Parvalbumin expression in AI, changes to the gene expression profiles of PV neurons, and an overall reduction in the inhibitory output of PV neurons. These changes are not mirrored in another population of neurons called Somatostatin-expressing interneurons. I show that deficits in gap detection behavior following hearing loss can be rescued by Chemogenetic activation of PV neurons in AI.