Using Sensory Processing to Identify Neural Circuit Deficits and Novel Treatment Strategies in a Rat Model of TSC
Abstract
Tuberous sclerosis complex (TSC) is a common and often debilitating neurodevelopmental disorder characterized by a host of behavioral and cognitive impairments collectively termed TSC-Associated Neuropsychiatric Disorders (TAND). TAND constitute some of the most disabling and quality of life affecting TSC symptoms, yet little is known about the brain disturbances that result in TAND. The focus of this proposal is on understanding TAND features and developing novel therapies for their treatment. Emerging evidence suggests that many TAND symptoms may arise from dysfunction at the neural circuit level, that is, in how neurons connect and communicate with each other to process incoming information. However, it has been difficult to link neural circuit deficits to specific clinical symptoms in TSC, which has limited our understanding of TAND mechanisms and impeded development of circuit-based therapies. This proposal will use novel sensory assays to examine neural circuit dysfunction and information processing deficits in a Tsc2+/- Eker rat model of TSC. Specifically, we will test the hypothesis that Tsc2+/- animals exhibit hyperexcitability in central auditory circuits that leads to sound hypersensitivity and auditory processing impairments and use these novel sensory symptoms as a platform for screening potential TSC and TAND therapies. Characterization of auditory impairments in Tsc2+/- animals may also shed light on to how brain function is altered more generally in TSC, providing crucial insight to the brain pathology that manifests as the diverse behavioral and cognitive symptoms of TSC and TAND.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310275
Entities
People
- Benjamin Auerbach
Organizations
- United States Army
- University of Illinois Urbana–Champaign