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 journalArticle

37 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 Sep 1
Externally publishedYes

ASJC Scopus subject areas

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

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