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Scientific Discovery and the Future of Medicine
May 26, 2015

Optogenetics and the Circuit Dynamics of Psychiatric Disease

Author Affiliations
  • 1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California
  • 2Department of Bioengineering, Stanford University, Stanford, California
  • 3Howard Hughes Medical Institute, Stanford University, Stanford, California
JAMA. 2015;313(20):2019-2020. doi:10.1001/jama.2015.2544

Optogenetics is a method for delivering millisecond-precision control (for activation or inhibition) to targeted cells using light within freely behaving mammals.1 The components of this method, as practiced today, involve (1) lasers and fiber optics for light delivery into the nervous system and (2) genes called microbial opsins, which encode light-activated proteins that regulate transmembrane ion conductance (Figure). Microbial opsins display diverse color sensitivity and conductance properties, with diversity generated by mutagenesis or arising naturally in the biosphere. Constituted by single genes, these microbial opsins can be targeted using a toolbox of genetic techniques, thereby specifying light-induced current flow in cells defined by function (eg, with excitatory, inhibitory, or dopaminergic properties) and anatomy (eg, with cell bodies in one location and projections going to another specific location across the brain). Light guidance with versatile fiber optics or spatial light modulators allows further resolution. Rapid advances in materials and electrical engineering have enabled opsin activation in neural tissue wirelessly using tiny LEDs.

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