Cellular mechanisms of auditory processing deficits in a mouse model of Fetal Alcohol Spectrum Disorders

Project Summary/Abstract Exposure to alcohol during pregnancy produces fetal alcohol spectrum disorders (FASD) that are associated with sensory and cognitive deficits. Individuals with FASD have impaired auditory processing and frequently exhibit atypical auditory behaviors. Developmental alcohol exposure has been shown to cause impairments in neuronal plasticity and GABAergic interneuron dysfunction. Parvalbumin expressing GABAergic interneurons are surrounded by perineuronal nets that regulate their development and plasticity. However, it is not known whether altered development of perineuronal nets and maturation of parvalbumin interneurons contribute to altered inhibition and changes in the network excitation in the auditory system in mice prenatally exposed to alcohol resulting in impairments in auditory processing. Here, we will use a mouse model of maternal voluntary alcohol consumption throughout gestation to examine the functionality of the central auditory pathway, identify region specific deficits in perineuronal nets and parvalbumin interneurons in the auditory system, examine synaptic inhibition in the primary auditory cortex and inferior colliculus, and investigate hyperexcitability in the primary auditory cortex in vivo. The goal of the proposal is to understand the effects of prenatal alcohol exposure sustained across gestation on auditory processing and identify auditory structures and cellular correlates that contribute to the auditory impairments.