A challenge for both basic and clinical neuroscience is the complexity of brain structure and function which makes it difficult to determine how electrical activity within individual cells causes behavior. Deisseroth adapted light-activated proteins from microbes (including the channelrhodopsins) to allow individual types of cells to be controlled with light in real time during behavior. The initial paper from Deisseroth’s lab, along with graduate students Feng Zhang (who received a Canada Gairdner International Award in 2016) and Edward Boyden, identified a key piece of the puzzle: channelrhodopsin-based control of neurons with light. Subsequently Deisseroth’s group designed the necessary tools for targeting opsins and light to circuit elements of interest and applied the final resulting method (optogenetics) to discover principles of brain function in health and disease.
Of equal importance, his group discovered the fundamental principles of the unique channelrhodopsin proteins in molecular detail by a wide range of genomic, biophysical, electrophysiological and structural techniques with many mutants in close collaboration with Peter Hegemann. This led to their deciphering of the unprecedented light-gated ion channel mechanism including its pore gating by photons and its ion selectivity. This basic work also fundamentally enabled optogenetics (the technology wherein light-activated proteins– first and foremost channelrhodopsin- allow control of selected cells within systems as complex as the mammalian brain, with unprecedented precision in space and time by delivery of light).
Optogenetics has been successfully employed to enhance our understanding of neural circuit function mediating normal behavior and dysfunction underlying neurological and psychiatric disorders. Optogenetics is a technology that has revolutionized the field of neuroscience and has enabled a new generation of experiments that probe the causal roles of specific neural circuit components.