A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing.

Abstract:

:Cell type-specific expression of optogenetic molecules allows temporally precise manipulation of targeted neuronal activity. Here we present a toolbox of four knock-in mouse lines engineered for strong, Cre-dependent expression of channelrhodopsins ChR2-tdTomato and ChR2-EYFP, halorhodopsin eNpHR3.0 and archaerhodopsin Arch-ER2. All four transgenes mediated Cre-dependent, robust activation or silencing of cortical pyramidal neurons in vitro and in vivo upon light stimulation, with ChR2-EYFP and Arch-ER2 demonstrating light sensitivity approaching that of in utero or virally transduced neurons. We further show specific photoactivation of parvalbumin-positive interneurons in behaving ChR2-EYFP reporter mice. The robust, consistent and inducible nature of our ChR2 mice represents a significant advance over previous lines, and the Arch-ER2 and eNpHR3.0 mice are to our knowledge the first demonstration of successful conditional transgenic optogenetic silencing. When combined with the hundreds of available Cre driver lines, this optimized toolbox of reporter mice will enable widespread investigations of neural circuit function with unprecedented reliability and accuracy.

journal_name

Nat Neurosci

journal_title

Nature neuroscience

authors

Madisen L,Mao T,Koch H,Zhuo JM,Berenyi A,Fujisawa S,Hsu YW,Garcia AJ 3rd,Gu X,Zanella S,Kidney J,Gu H,Mao Y,Hooks BM,Boyden ES,Buzsáki G,Ramirez JM,Jones AR,Svoboda K,Han X,Turner EE,Zeng H

doi

10.1038/nn.3078

subject

Has Abstract

pub_date

2012-03-25 00:00:00

pages

793-802

issue

5

eissn

1097-6256

issn

1546-1726

pii

nn.3078

journal_volume

15

pub_type

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