Integrated Brainwide Structural and Functional Analysis
Karl Deisseroth, Stanford University
This talk will address optical tools for precise, high-resolution investigation of intact biological systems, and application of these tools to study the neural circuit underpinnings of adaptive and maladaptive behavior. Over the past eleven years we have developed both optogenetics (a technology for precisely controlling millisecond-scale activity patterns in specific cell types using microbial opsin genes and fiberoptic-based neural interfaces) and CLARITY (a technology to optically resolve high-resolution structural and molecular detail within intact tissues without disassembly). Most recently in optogenetics, our team has developed strategies for targeting microbial opsins and light to meet the challenging constraints of the freely-behaving mammal, engineered a panel of microbial opsin genes spanning a range of optical and kinetic properties, built high-speed behavioral and neural activity-readout tools compatible with real-time optogenetic control, and applied these optogenetic tools to develop circuit-based insight into anxiety, depression, and motivated behaviors. With CLARITY, whole mouse brains have now been labeled and imaged, and molecular markers have been used to identify individual structures and projections in banked human brain tissue, thereby unlocking rich sources of information for probing disease mechanisms as well as the native structure and complexity of the nervous system, in a manner complementary to optogenetic approaches.