Molecular and Cellular Approaches for Diversifying and Extending Optogenetics

Viviana Gradinaru, Feng Zhang, Charu Ramakrishnan, Joanna Mattis, Rohit Prakash, Ilka Diester, Inbal Goshen, Kimberly R. Thompson, Karl Deisseroth*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

797 Scopus citations

Abstract

Optogenetic technologies employ light to control biological processes within targeted cells in vivo with high temporal precision. Here, we show that application of molecular trafficking principles can expand the optogenetic repertoire along several long-sought dimensions. Subcellular and transcellular trafficking strategies now permit (1) optical regulation at the far-red/infrared border and extension of optogenetic control across the entire visible spectrum, (2) increased potency of optical inhibition without increased light power requirement (nanoampere-scale chloride-mediated photocurrents that maintain the light sensitivity and reversible, step-like kinetic stability of earlier tools), and (3) generalizable strategies for targeting cells based not only on genetic identity, but also on morphology and tissue topology, to allow versatile targeting when promoters are not known or in genetically intractable organisms. Together, these results illustrate use of cell-biological principles to enable expansion of the versatile fast optogenetic technologies suitable for intact-systems biology and behavior.

Original languageAmerican English
Pages (from-to)154-165
Number of pages12
JournalCell
Volume141
Issue number1
DOIs
StatePublished - Apr 2010
Externally publishedYes

Bibliographical note

Funding Information:
V.G. is supported by the Stanford Interdisciplinary Graduate Fellowship, F.Z. by the National Institutes of Health (NIH) and Harvard Society of Fellows, J.M. by the Stanford Medical Scientist Training Program, R.P. by the NIH, I.D. by the German Academic Exchange Service and the Human Frontier Science Program, I.G. by the Machiah Foundation and the Weizmann Institute, K.T. by the National Alliance for Research on Schizophrenia and Depression, and K.D. by the Woo, Keck, Snyder, McKnight, Yu, and Coulter Foundations, as well as by the California Institute of Regenerative Medicine, the National Science Foundation, and the NIH. We thank the entire Deisseroth lab for their support.

Keywords

  • Molneuro
  • Sysneuro

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