A switch for manipulating active neurons


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You have full access to this article via your institution. Download PDF Lee, D. _et al_. _Nat. Biotechnol._ http://dx.doi.org/10.1038/nbt.3902 (2017). Immediate early gene promoters such as


that for _c-Fos_ have been used to manipulate gene expression in response to neural activity. However, this approach provides an indirect and approximate representation of neuronal activity.


Lee _et al_. report Cal-Light, a calcium- and light-dependent switch that drives gene expression in activated neurons. Upon calcium accumulation during neuronal activity and concurrent


blue-light illumination, TEV protease is reconstituted from two fragments via a calcium-dependent interaction between calmodulin and the peptide M13; at the same time, a TEV cleavage site is


revealed in a light-dependent manner and cleaved by the reconstituted TEV protease. This cleavage releases the transcriptional activator tTA, which can then turn on the expression of a


reporter or other gene of interest. The researchers use the Cal-Light switch to drive expression of halorhodopsin in neurons activated in mice during a lever-pressing reinforcement task. The


researchers found that inhibiting these neurons then impaired the learned behavior in these mice. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE A


switch for manipulating active neurons. _Nat Methods_ 14, 768 (2017). https://doi.org/10.1038/nmeth.4375 Download citation * Published: 01 August 2017 * Issue Date: 01 August 2017 * DOI:


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