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Auditory Cortex Processing in Developmental and Adult Plasticity: Implications in Fragile X Syndrome

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Neurodevelopmental disorders (NDD) are a large body of disorders that together affect 1 in 6 children in the U.S. (Center for Disease Control and Prevention). They are characterized by deficits in communication, cognition, attention, socialization and behavior. Abnormalities in sensory processing are also prevalent, and may underlie higher-order processing such as multisensory integration and perception. Determining a root cause in any one NDD is conflated by the multiplicity of brain regions affected, divergence of behavioral outcome measures in animal models and humans, and the multiple mechanistic underpinnings.

Targeting basic sensory processing in NDD is an approach that may address some of these problems. Sensory processing deficits, including auditory, somatosensory, motor and visual, are common in NDDs. While sensory processing may seem far removed from a concept like behavior or socialization, basic sensory processing does serve as the foundation for cognition. Sensory information is relayed to multisensory and emotion-regulation regions of the brain which allow organisms to associate emotional states and salience to sensory information. Learning and memory events such as operant or appetitive conditioning induce stable modifications of processing in sensory regions of the brain, while loss of sensory function can affect working memory and attention. This indicates that disordered sensory processing in fact can affect an organism on multiple levels of function. Understanding the development of basic sensory processing and targeting specific developmental mechanisms may rescue processing deficits in NDD, with the potential for improvements in perception and ‘higher-order’ cognition.

In this series of studies, I focused on the auditory system and sought to increase our understanding of auditory cortex development, and its implications for adult behaviors in a fragile X Syndrome (FXS) mouse model. I discovered the developmental expression patterns of an array of proteins in both early and adult auditory cortex. I discovered differential regulation of proteins within sub-regions of auditory cortex in response to developmental plasticity. I further discovered that dysregulation of these same proteins in adult FXS mice impairs memory formation. Results point to a particular role for perineuronal nets in auditory cortex development and in adult plasticity.

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