Grant: Foundation Grant

The primary goal of my research is to understand how brain circuits form during early development and how mutations and errors give rise to dysfunctional circuits that underlie common neurodevelopmental disorders such as Autism Spectrum Disorders (ASD) and Epilepsy. The distinctive feature of our research approach is the development of multi-disciplinary and highly innovative imaging tools that combine electrophysiology, genetics and technology development in microscope design to see brain neural network activity and growth. In addition to the development of these tools, I also developed a leading model of vertebrate brain circuit formation by taking advantage of the unique development features of the albino Xenopus tadpole. Specifically, the external development and transparency of the embryos allows us to directly image brain circuit formation in live animals. Another example of our novel approach involves labeling individual brain neurons using single-cell electroporation, a technique I invented to tag neurons and control their gene expression so that we can image 3D growth in real time using ultrafast microscopes constructed in my lab. Our research has demonstrated that neural activity in response to external stimuli guides neuronal growth and connectivity in a manner that allows for self-organization and optimization in processing the input encountered during development. Our findings on brain circuit formation have provided important insight into the origins of ASD where a large proportion of associated gene mutations disrupt the function of synaptic proteins. We also created single-cell models of ASD to express mutant genes in order to test alterations in growth, synapse formation and encoding. In parallel, we study Epilepsy to test whether seizures hijack activity-driven growth events. Once we understand how normal and dysfunctional brain circuits are formed, we will develop and evaluate new interventions for preventative and corrective treatments.