Texas Children's Hospital

Intellectual disabilities and autism spectrum disorders (lD/ASDs) represent a huge health care burden.  Dozens of genes that perform diverse molecular functions have been shown to cause these disorders when mutated, deleted or duplicated.  The challenge is to understand how such disparate molecular changes result in similar phenotypes and how we can treat these disorders given their genetic heterogeneity.  The investigators’ overarching hypothesis is that diverse molecular changes alter neural network activity and synaptic homeostasis; that such alterations in network activity lead to the overlapping cognitive and motor phenotypes; and that manipulating the aberrant activity, through modalities such as deep brain stimulation (DBS), will prove effective in treating this broad class of disorders.  They will investigate neural circuit dysfunction and treatment response in genetically-accurate models of ID/ASDs.  Specifically, they will determine the neural circuit activity in genetic models of Rett and Angelman syndromes using in vivo recordings of single units, synaptic plasticity, and network oscillations in freely-moving mice for each disease model.  They will then relate the circuit abnormalities to the cognitive deficits of these mice, and finally, will use DBS to explore possible therapeutic intervent.