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Neuron. 2015 Mar 4;85(5):942-58. doi: 10.1016/j.neuron.2015.02.022.

Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance.

Author information

1
Allen Institute for Brain Science, 551 N 34(th) Street, Seattle, WA 98103, USA.
2
UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
3
MIT Media Lab and McGovern Institute, Massachusetts Institute of Technology, 20 Ames Street, Cambridge, MA 02139, USA.
4
Brain Research Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
5
Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan.
6
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
7
UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK; Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan.
8
Department of Physiology, Brain Health Research Centre, University of Otago, PO Box 913, Dunedin 9054, New Zealand.
9
The Division of Brain Sciences, Department of Medicine, Imperial College London, 160 DuCane Road, London, W12 0NN, UK.
10
Allen Institute for Brain Science, 551 N 34(th) Street, Seattle, WA 98103, USA. Electronic address: hongkuiz@alleninstitute.org.

Abstract

An increasingly powerful approach for studying brain circuits relies on targeting genetically encoded sensors and effectors to specific cell types. However, current approaches for this are still limited in functionality and specificity. Here we utilize several intersectional strategies to generate multiple transgenic mouse lines expressing high levels of novel genetic tools with high specificity. We developed driver and double reporter mouse lines and viral vectors using the Cre/Flp and Cre/Dre double recombinase systems and established a new, retargetable genomic locus, TIGRE, which allowed the generation of a large set of Cre/tTA-dependent reporter lines expressing fluorescent proteins, genetically encoded calcium, voltage, or glutamate indicators, and optogenetic effectors, all at substantially higher levels than before. High functionality was shown in example mouse lines for GCaMP6, YCX2.60, VSFP Butterfly 1.2, and Jaws. These novel transgenic lines greatly expand the ability to monitor and manipulate neuronal activities with increased specificity.

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PMID:
25741722
PMCID:
PMC4365051
DOI:
10.1016/j.neuron.2015.02.022
[Indexed for MEDLINE]
Free PMC Article

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