Understanding how brain cells give rise to complex processes like action, thought, and emotion is limited by the current availability of tools to control specific cells within neural tissue. Fast, genetically targeted control over brain cells would allow elucidation of the role of specific neuronal types, and greatly advance our understanding of brain function. To enable precise perturbation of living circuits, the light-activated ion channel, called channelrhodopsin-2 (ChR2), will be used for genetically targeted, millisecond-timescale optical excitation of neurons. Another protein, called NpHR, has been identified for temporally-precise optical inhibition of neural activity. Both proteins function in mammalian neurons, together forming a complete, complementary system for multimodal, high-speed, genetically-targeted, all-optical investigation of living neural circuits.
This project encompasses a broad technology development, testing, and dissemination plan that will yield generalizable, powerful tools for the physiology, neuroscience and biomedical engineering communities. Specifically, high-speed optical imaging reagents and technology for simultaneous imaging and optical stimulation/inhibition will be developed, in living animals. This is a fundamentally novel approach that could revolutionize the way circuits are probed in intact neural systems. These tools have an enormous range of applications, and the outcome of this work may be versatile enough to allow investigators to determine the contribution of a cell type of choice and relate it to circuit dynamics and behavior in virtually any brain region of interest. These new technologies also afford unique training opportunities for students, who will move on to other institutions and pass on expertise, leading over years to generation of a widespread cadre of scientists and engineers with intensive training in this powerful technology.
