A calcium- A nd light-gated switch to induce gene expression in activated neurons

Dongmin Lee, Jung Ho Hyun, Kanghoon Jung, Patrick Hannan, Hyung Bae Kwon

Research output: Contribution to journalArticlepeer-review

94 Citations (Scopus)

Abstract

Despite recent advances in optogenetics, it remains challenging to manipulate gene expression in specific populations of neurons. We present a dual-protein switch system, Cal-Light, that translates neuronal-activity-mediated calcium signaling into gene expression in a light-dependent manner. In cultured neurons and brain slices, we show that Cal-Light drives expression of the reporter EGFP with high spatiotemporal resolution only in the presence of both blue light and calcium. Delivery of the Cal-Light components to the motor cortex of mice by viral vectors labels a subset of excitatory and inhibitory neurons related to learned lever-pressing behavior. By using Cal-Light to drive expression of the inhibitory receptor halorhodopsin (eNpHR), which responds to yellow light, we temporarily inhibit the lever-pressing behavior, confirming that the labeled neurons mediate the behavior. Thus, Cal-Light enables dissection of neural circuits underlying complex mammalian behaviors with high spatiotemporal precision.

Original languageEnglish
Pages (from-to)858-863
Number of pages6
JournalNature Biotechnology
Volume35
Issue number9
DOIs
Publication statusPublished - 2017 Sept 1
Externally publishedYes

Bibliographical note

Funding Information:
We would like to thank B. Kuhlman (University of North Carolina, Chapel Hill) for iLID construct; K. Deisseroth (Stanford University) for an eNpHR-EYFP construct; C. Tucker (University of Colorado) for CRY2 and CIBN constructs; H. Zeng (Allen institute) for a TetO-EGFP construct; S-Y. Choi (Chonnam National University, Republic of Korea) for a P2A vector; W. Weber (University of Freiburg, Germany) for a pSAM200 vector. We thank K-S. Lee and D. Fitzpatrick for helping 3D reconstruction of neurons. We thank M.J. Yetman and H. Taniguchi for helping antibody staining and resource sharing. We thank Y. Chen and B.L. Sabatini for testing initial Cal-Light constructs. We thank all members of the laboratory for critical discussion and comments. This work was supported by funding from a Korea University Grant (to D.L.) and Max Planck Florida Institute for Neuroscience (to H.-B.K.). DNA plasmids used in this study have been deposited to Addgene (Deposit number: 74208).

Publisher Copyright:
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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