Development of next-generation optical neural silencers

[摘要] 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.

[发布机构] Massachusetts Institute of Technology