Autism, epilepsy & schizophrenia

Non-Invasive Optogenetic Engineering of Cortical Dynamics
2013 Seed Grant
Brian Chow, Ph.D.
Department of Bioengineering
University of Pennsylvania

The goal of Dr. Chow’s project is to create the tools and methodology for disrupting cortical excitatory/inhibitory balance via non-invasive optogenetic perturbation. Disrupted E/I balance is thought play a pathophysiological role in nervous system disorders of high unmet clinical need such as schizophrenia and autism spectrum disorders, epilepsy, among others (Eichler et al, Front. Mol. Neuro. 2008 and references within). ┬áRecent optogenetic studies confirmed that E/I imbalance can lead to social deficit phenotypes in rodents, a phenotype of observed in patients with schizophrenia and autism spectrum disorders (Yizhar et al. Nature, 2011). ┬áThus, understanding this balance is both critical to treating CNS disorder and tractable for via optogenetic manipulation. By combining the 2-dimensional control of light delivery, with in utero electroporation for layer-specific transgene expression, if successful, Dr. Chow will create the ability to selectively manipulate neurons with 3-dimensional complexity non-invasively in freely behaving animals.