Defining the Developmental Time Course and Therapeutic Window for Sensory Circuit Impairments in a Rat Model of Fragile X Syndrome
Abstract
Central auditory processing disruptions are some of the most common and debilitating features of autism spectrum disorders (ASD) and related neurodevelopmental disorders like Fragile X Syndrome (FXS). Despite the prevalence and severity of auditory disruptions in FXS and ASD, we are only beginning to understand their underlying brain mechanisms. A major unresolved question is how sensory disturbances in FXS and ASD emerge during development. Intriguingly, early-life sensory deficits in FXS and ASD have been shown to be predictive of the development and severity of behavioral and cognitive symptoms in adulthood. Thus, understanding the developmental mechanisms of auditory processing deficits in FXS will not only directly impact this clinically important sensory symptom, but may extend to other behavioral and cognitive domains as well. The goal of the current project is to identify when and where auditory dysfunction emerges in FXS. Identifying the sequence of events that leads to central auditory processing deficits in FXS is critical for determining optimal windows for initiation of treatments in FXS and related neurodevelopmental disorders. This proposal will address this need by determining the developmental time-course of central auditory processing deficits a Fmr1KO rat model of FX, which we have recently shown to exhibit sound hypersensitivity and central auditory hyperactivity in adulthood. In addition, we will systematically investigate the effectiveness of pharmacological, environmental, and combined intervention during critical developmental time windows using the robust auditory behavioral and neurophysiological phenotypes that we have previously characterized in adult Fmr1KO rats. This work has the potential to provide important insight into the development of central auditory processing disruptions in FXS and other autism-related disorders, which will be crucial for guiding future clinical treatment studies and pre-clinical screening of novel therapies.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310395
Entities
People
- Benjamin Auerbach
Organizations
- United States Army
- University of Illinois Urbana–Champaign