Genetically targeted all-optical electrophysiology with a transgenic cre-dependent optopatch mouse

Shan Lou; Yoav Adam; Eli N. Weinstein; Erika Williams; Katherine Williams; Vicente Parot; Nikita Kavokine; Stephen Liberles; Linda Madisen; Hongkui Zeng; Adam E. Cohen

doi:10.1523/JNEUROSCI.1582-16.2016

Genetically targeted all-optical electrophysiology with a transgenic cre-dependent optopatch mouse

Shan Lou, Yoav Adam, Eli N. Weinstein, Erika Williams, Katherine Williams, Vicente Parot, Nikita Kavokine, Stephen Liberles, Linda Madisen, Hongkui Zeng, Adam E. Cohen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

Abstract

Recent advances in optogenetics have enabled simultaneous optical perturbation and optical readout of membrane potential in diverse cell types. Here, we develop and characterize a Cre-dependent transgenic Optopatch2 mouse line that we call Floxopatch. The animals expressed a blue-shifted channelrhodopsin, CheRiff, and a near infrared Archaerhodopsin-derived voltage indicator, QuasAr2, via targeted knock-in at the rosa26 locus. In Optopatch-expressing animals, we tested for overall health, genetically targeted expression, and function of the optogenetic components. In offspring of Floxopatch mice crossed with a variety of Cre driver lines, we observed spontaneous and optically evoked activity in vitro in acute brain slices and in vivo in somatosensory ganglia. Cell-type-specific expression allowed classification and characterization of neuronal subtypes based on their firing patterns. The Floxopatch mouse line is a useful tool for fast and sensitive characterization of neural activity in genetically specified cell types in intact tissue.

Original language	American English
Pages (from-to)	11059-11073
Number of pages	15
Journal	Journal of Neuroscience
Volume	36
Issue number	43
DOIs	https://doi.org/10.1523/JNEUROSCI.1582-16.2016
State	Published - 26 Oct 2016
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by the Howard Hughes Medical Institute, the Allen Institute for Brain Science, and GlaxoSmithKline (Bioelectronic Medicines Initiative Grant). A.E.C. is supported by National Institutes of Health (NIH) Grant 1-R01-EB012498. Y.A. is supported by a long-term fellowship of the Human Frontier Science Program. E.W. is supported by NIH Grants F30CA177170 and T32GM007753. S. Liberles is supported by NIH Grant DK103703. We thank Vaibhav Joshi and Melinda Lee for technical assistance. We thank Qiufu Ma, Xinzhong Dong, Rohini Kuner, Venkatesh Murthy, and Paola Arlotta for scientific discussions and for sharing Cre driver mouse lines; Corey Smith, Stephen Lewis, and Paulina Getsy for training and assistance; the Harvard University Genome Modification Facility for technical support in generating transgenic mice; and the Harvard Center for Brain Sciences for providing confocal imaging facilities.

Publisher Copyright:
© 2016 the authors.

Keywords

Optogenetics
Optopatch
Transgenic mice
Voltage imaging

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10.1523/JNEUROSCI.1582-16.2016

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title = "Genetically targeted all-optical electrophysiology with a transgenic cre-dependent optopatch mouse",

abstract = "Recent advances in optogenetics have enabled simultaneous optical perturbation and optical readout of membrane potential in diverse cell types. Here, we develop and characterize a Cre-dependent transgenic Optopatch2 mouse line that we call Floxopatch. The animals expressed a blue-shifted channelrhodopsin, CheRiff, and a near infrared Archaerhodopsin-derived voltage indicator, QuasAr2, via targeted knock-in at the rosa26 locus. In Optopatch-expressing animals, we tested for overall health, genetically targeted expression, and function of the optogenetic components. In offspring of Floxopatch mice crossed with a variety of Cre driver lines, we observed spontaneous and optically evoked activity in vitro in acute brain slices and in vivo in somatosensory ganglia. Cell-type-specific expression allowed classification and characterization of neuronal subtypes based on their firing patterns. The Floxopatch mouse line is a useful tool for fast and sensitive characterization of neural activity in genetically specified cell types in intact tissue.",

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note = "Funding Information: This work was supported by the Howard Hughes Medical Institute, the Allen Institute for Brain Science, and GlaxoSmithKline (Bioelectronic Medicines Initiative Grant). A.E.C. is supported by National Institutes of Health (NIH) Grant 1-R01-EB012498. Y.A. is supported by a long-term fellowship of the Human Frontier Science Program. E.W. is supported by NIH Grants F30CA177170 and T32GM007753. S. Liberles is supported by NIH Grant DK103703. We thank Vaibhav Joshi and Melinda Lee for technical assistance. We thank Qiufu Ma, Xinzhong Dong, Rohini Kuner, Venkatesh Murthy, and Paola Arlotta for scientific discussions and for sharing Cre driver mouse lines; Corey Smith, Stephen Lewis, and Paulina Getsy for training and assistance; the Harvard University Genome Modification Facility for technical support in generating transgenic mice; and the Harvard Center for Brain Sciences for providing confocal imaging facilities. Publisher Copyright: {\textcopyright} 2016 the authors.",

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doi = "10.1523/JNEUROSCI.1582-16.2016",

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AU - Adam, Yoav

AU - Weinstein, Eli N.

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AU - Parot, Vicente

AU - Kavokine, Nikita

AU - Liberles, Stephen

AU - Madisen, Linda

AU - Zeng, Hongkui

AU - Cohen, Adam E.

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N2 - Recent advances in optogenetics have enabled simultaneous optical perturbation and optical readout of membrane potential in diverse cell types. Here, we develop and characterize a Cre-dependent transgenic Optopatch2 mouse line that we call Floxopatch. The animals expressed a blue-shifted channelrhodopsin, CheRiff, and a near infrared Archaerhodopsin-derived voltage indicator, QuasAr2, via targeted knock-in at the rosa26 locus. In Optopatch-expressing animals, we tested for overall health, genetically targeted expression, and function of the optogenetic components. In offspring of Floxopatch mice crossed with a variety of Cre driver lines, we observed spontaneous and optically evoked activity in vitro in acute brain slices and in vivo in somatosensory ganglia. Cell-type-specific expression allowed classification and characterization of neuronal subtypes based on their firing patterns. The Floxopatch mouse line is a useful tool for fast and sensitive characterization of neural activity in genetically specified cell types in intact tissue.

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KW - Voltage imaging

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JO - Journal of Neuroscience

JF - Journal of Neuroscience

IS - 43

ER -

Genetically targeted all-optical electrophysiology with a transgenic cre-dependent optopatch mouse

Abstract

Bibliographical note

Keywords

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