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

Linda Madisen, Aleena R. Garner, Daisuke Shimaoka, Amy S. Chuong, Nathan C. Klapoetke, Lu Li, Alexander van der Bourg, Yusuke Niino, Ladan Egolf, Claudio Monetti, Hong Gu, Maya Mills, Adrian Cheng, Bosiljka Tasic, Thuc Nghi Nguyen, Susan M. Sunkin, Andrea Benucci, Andras Nagy, Atsushi Miyawaki, Fritjof Helmchen & 6 others Ruth M. Empson, Thomas Knöpfel, Edward S. Boyden, R. Clay Reid, Matteo Carandini, Hongkui Zeng

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)942-958
Number of pages17
JournalNeuron
Volume85
Issue number5
DOIs
Publication statusPublished - 4 Mar 2015
Externally publishedYes

Cite this

Madisen, Linda ; Garner, Aleena R. ; Shimaoka, Daisuke ; Chuong, Amy S. ; Klapoetke, Nathan C. ; Li, Lu ; van der Bourg, Alexander ; Niino, Yusuke ; Egolf, Ladan ; Monetti, Claudio ; Gu, Hong ; Mills, Maya ; Cheng, Adrian ; Tasic, Bosiljka ; Nguyen, Thuc Nghi ; Sunkin, Susan M. ; Benucci, Andrea ; Nagy, Andras ; Miyawaki, Atsushi ; Helmchen, Fritjof ; Empson, Ruth M. ; Knöpfel, Thomas ; Boyden, Edward S. ; Reid, R. Clay ; Carandini, Matteo ; Zeng, Hongkui. / Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance. In: Neuron. 2015 ; Vol. 85, No. 5. pp. 942-958.
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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.",
author = "Linda Madisen and Garner, {Aleena R.} and Daisuke Shimaoka and Chuong, {Amy S.} and Klapoetke, {Nathan C.} and Lu Li and {van der Bourg}, Alexander and Yusuke Niino and Ladan Egolf and Claudio Monetti and Hong Gu and Maya Mills and Adrian Cheng and Bosiljka Tasic and Nguyen, {Thuc Nghi} and Sunkin, {Susan M.} and Andrea Benucci and Andras Nagy and Atsushi Miyawaki and Fritjof Helmchen and Empson, {Ruth M.} and Thomas Kn{\"o}pfel and Boyden, {Edward S.} and Reid, {R. Clay} and Matteo Carandini and Hongkui Zeng",
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Madisen, L, Garner, AR, Shimaoka, D, Chuong, AS, Klapoetke, NC, Li, L, van der Bourg, A, Niino, Y, Egolf, L, Monetti, C, Gu, H, Mills, M, Cheng, A, Tasic, B, Nguyen, TN, Sunkin, SM, Benucci, A, Nagy, A, Miyawaki, A, Helmchen, F, Empson, RM, Knöpfel, T, Boyden, ES, Reid, RC, Carandini, M & Zeng, H 2015, 'Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance' Neuron, vol. 85, no. 5, pp. 942-958. https://doi.org/10.1016/j.neuron.2015.02.022

Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance. / Madisen, Linda; Garner, Aleena R.; Shimaoka, Daisuke; Chuong, Amy S.; Klapoetke, Nathan C.; Li, Lu; van der Bourg, Alexander; Niino, Yusuke; Egolf, Ladan; Monetti, Claudio; Gu, Hong; Mills, Maya; Cheng, Adrian; Tasic, Bosiljka; Nguyen, Thuc Nghi; Sunkin, Susan M.; Benucci, Andrea; Nagy, Andras; Miyawaki, Atsushi; Helmchen, Fritjof; Empson, Ruth M.; Knöpfel, Thomas; Boyden, Edward S.; Reid, R. Clay; Carandini, Matteo; Zeng, Hongkui.

In: Neuron, Vol. 85, No. 5, 04.03.2015, p. 942-958.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Helmchen, Fritjof

AU - Empson, Ruth M.

AU - Knöpfel, Thomas

AU - Boyden, Edward S.

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AU - Carandini, Matteo

AU - Zeng, Hongkui

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