2019 New Initiative Grant
Michael Platt, Ph.D. (PI) Neuroscience, Professor of Psychology, and Professor of Marketing, University of Pennsylvania
Maria Geffen, Ph.D. (co-investigator) Associate Professor of Otorhinolaryngology, Associate Professor of Neuroscience and Associate Professor of Neurology, University of Pennsylvania
Brian Litt, Ph.D. (co-investigator) Professor of Neurology, Professor of Neurosurgery, and Professor of Bioengineering, University of Pennsylvania
Optimizing optogenetics in the primate brain
Abstract
Optogenetics is a revolutionary technique in neuroscience. By combining light-sensitive proteins with intracranial light delivery, optogenetics offers researchers unprecedented control over neuronal activity in the brain. The technique has become the dominant approach for studying neural circuits in small animal models such as mice and flies. Unfortunately, optogenetics has so far failed to have a major impact on research using larger animals more similar to humans, such as monkeys. A major limiting factor is the sheer size of the primate brain, which is 200 times bigger than the mouse brain, thus posing challenges for both gene transfection and light delivery. Until these challenges are solved, the promise of optogenetics for both understanding higher-order cognition and treating neurological and psychiatric disorders in humans will remain unrealized. Our multidisciplinary team of investigators proposes to overcome these obstacles by combining three new technologies: ultra-sensitive inhibitory opsins, convection-enhanced delivery of genes, and wireless light stimulation with chronically implantable LED arrays. This approach will finally allow us to control behaviorally meaningful volumes of the primate brain in animals free of any physical restraint and thus permit causal dissection of the neural circuits that mediate naturally-occurring primate behaviors relevant for understanding and treating human brain disorders.