Prosthetic systems for therapeutic optical activation and silencing of genetically-targeted neurons
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Bernstein, J. G., Han, X., Henninger, M. A., Ko, E. Y., Qian, X., Franzesi, G. T., McConnell, J. P., Stern, P., Desimone, R., and Boyden, E. S. (2008) Prosthetic systems for therapeutic optical activation and silencing of genetically-targeted neurons, Proc Soc Photo Opt Instrum Eng 6854:68540H.
Many neural disorders are associated with aberrant activity in specific cell types or neural projection pathways embedded within the densely-wired, heterogeneous matter of the brain. An ideal therapy would permit correction of activity just in specific target neurons, while leaving other neurons unaltered. Recently our lab revealed that the naturally-occurring light-activated proteins channelrhodopsin-2 (ChR2) and halorhodopsin (Halo/NpHR) can, when genetically expressed in neurons, enable them to be safely, precisely, and reversibly activated and silenced by pulses of blue and yellow light, respectively. We here describe the ability to make specific neurons in the brain light-sensitive, using a viral approach. We also reveal the design and construction of a scalable, fully-implantable optical prosthetic capable of delivering light of appropriate intensity and wavelength to targeted neurons at arbitrary 3-D locations within the brain, enabling activation and silencing of specific neuron types at multiple locations. Finally, we demonstrate control of neural activity in the cortex of the non-human primate, a key step in the translation of such technology for human clinical use. Systems for optical targeting of specific neural circuit elements may enable a new generation of high-precision therapies for brain disorders.