"Development of structural and functional abnormalities underlying auditory hypersensitivity in a mouse model of Fragile X Syndrome"
Teresa Wen (Scripps ‘12; University of California, Riverside, Neuroscience Program)
Wednesday, April 4th, 4:30 PM, Burns Lecture Hall (RM B31), Keck Science Center
Abstract: Fragile X Syndrome (FXS) is a leading inherited cause of autism and intellectual disability. FXS occurs as a result Fmr1 gene hypermethylation, which leads to inactivation and loss of Fragile X Mental Retardation Protein (FMRP). Behavioral and functional studies of humans with FXS indicate auditory hypersensitivity, which is also evident in a mouse model of Fragile X Syndrome, the Fmr1 knockout (KO) mouse. In vivo electrophysiology data obtained from KO mouse primary auditory cortex (A1) indicates that adult neurons are hyperexcitable, exhibit increased variability in first spike latency, and have broader tuning. EEGs recorded in adult Fmr1 KO mice also exhibit baseline and stimulus-evoked cortical hyperexcitability. However the developmental trajectory of these phenotypes have not been studied. Moreover, the molecular mechanisms underlying this altered excitatory/inhibitory balance are unknown. In this study, we characterized developmental changes in neuronal response magnitudes, network excitability, and perineuronal net expression around GABAergic interneurons in Fmr1 KO auditory cortex. In Fmr1 KO auditory cortex, there is a transient reduction in perineuronal net expression around GABAergic interneurons which coincides with single neuron hyperexcitability. Moreover, developing KO cortex exhibits increased oscillatory gamma during rest. These findings suggest that FXS is associated with developmental impairments in cortical processing. Future therapeutics may be more beneficial if administered during a developmental critical period.
Burns Lecture Hall is located in the basement of the W.M. Keck Science Center, which is located on the corner of N. Mills Ave. and 9th St. Burns Lecture Hall is wheel chair accessible.
Thomas B. Borowski, Ph.D
Pitzer College IRB Chair