Development of Next-Generation Optical Neural Silencers

The ability to rapidly and safely silence the electrical activity of individual neurons or neuron populations is invaluable in the study of brain circuit mapping. The expression of light-driven ion channels and pumps allows these pathways to be observed, mapped and controlled with millisecond timescale resolution. We here show that it is possible to mediate the powerful multiple-color silencing of neural activity through the heterologous expression of light-driven outward proton pumps and inward chloride pumps. We characterized a number of novel opsins through an exploration of ecological and genomic diversity, and further boosted opsin function and trafficking through the appendage of signal sequences. The green-light drivable archaerhodopsin-3 (Arch) from Halorubrum sodomense and the yellow-light drivable archaerhodopsin from Halorubrum strain TP009 (ArchT) are able to mediate complete neuron silencing in the in vivo awake mouse brain, and the blue-light drivable proton pump from Leptosphaeria maculans (Mac) opens up the potential for the multiple-color control of independent neuron populations. Finally, the principles outlined here can be extrapolated to the larger context of synthetic physiology. Thesis Supervisor: Edward S. Boyden, III Benesse Career Development Professor Program in Media Arts and Sciences Reader: Hugh Herr, Ph.D. Associate Professor of Media Arts and Sciences MIT Program in Media Arts and Sciences