Fragile X Syndrome

Fragile X Syndrome (FXS) is the leading known genetic cause of autism spectrum disorder.  Despite the prevalence of FXS, its known relationship to autism, and known underlying genetic cause, progress towards treatment of FXS has been slow.

Individuals with FXS show symptoms of auditory hypersensitivity. These symptoms may arise due to sustained neural responses to repeated sounds, but the underlying neural mechanisms of these behaviors are not clear, and how potential drugs work at the neural systems level is also not known. Because complex behaviors do not easily translate across pre-clinical animal models and humans, an approach to a new paradigm of drug discovery that integrates cellular mechanisms with analogous neural responses in mice and humans is required.

Auditory processing in Fmr1 KO mice: sound evoked ERPs habituate less in KO mice

Our laboratory focuses on a multilevel, integrated approach that tests mechanisms of sensory neocortical dysfunction in FXS and pharmacological approaches to ameliorate deficits.  To this end, we use auditory event-related potentials (ERPs) and responses with in vivo electrophysiology and multielectrode array (MEA) analysis in wild-type and Fmr1 KO mice.  We aim to generate specific electrophysiological biomarkers of dysfunctional circuit responses to sound in FXS, and test hypothesized mechanisms of these deficits and novel pharmacological approaches based on a rational strategy.  We actively collaborate with several other research groups as part of an NIH-designated Fragile X Center  Thus, our research group is well integrated in bridging neurophysiological and pharmacological approaches across preclinical and clinical studies in a truly translational manner.

32 channel multielectrode array (MEA) at baseline