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Aberrant Cortical Activity In Multiple GCaMP6-Expressing Transgenic Mouse Lines

View ORCID ProfileNicholas A. Steinmetz, Christina Buetfering, View ORCID ProfileJerome Lecoq, View ORCID ProfileChristian R. Lee, View ORCID ProfileAndrew J. Peters, View ORCID ProfileElina A. K. Jacobs, View ORCID ProfilePhilip Coen, View ORCID ProfileDouglas R. Ollerenshaw, View ORCID ProfileMatthew T. Valley, View ORCID ProfileSaskia E. J. de Vries, Marina Garrett, Jun Zhuang, Peter A. Groblewski, Sahar Manavi, Jesse Miles, Casey White, Eric Lee, Fiona Griffin, Joshua D Larkin, Kate Roll, Sissy Cross, Thuyanh V. Nguyen, Rachael Larsen, Julie Pendergraft, Tanya Daigle, Bosiljka Tasic, Carol L. Thompson, Jack Waters, Shawn Olsen, David J. Margolis, Hongkui Zeng, Michael Hausser, Matteo Carandini, Kenneth D. Harris
doi: https://doi.org/10.1101/138511
Nicholas A. Steinmetz
1UCL Institute of Neurology; Department of Neuroscience, Physiology and Pharmacology; UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK
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  • ORCID record for Nicholas A. Steinmetz
  • For correspondence: nick.steinmetz@gmail.com
Christina Buetfering
2Wolfson Institute for Biomedical Research; Department of Neuroscience, Physiology and Pharmacology; University College London, London, UK
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Jerome Lecoq
3Allen Institute for Brain Science, Seattle WA, USA
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Christian R. Lee
4Rutgers, The State University of New Jersey, Department of Cell Biology and Neuroscience, Piscataway, New Jersey 08854, USA
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Andrew J. Peters
1UCL Institute of Neurology; Department of Neuroscience, Physiology and Pharmacology; UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK
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Elina A. K. Jacobs
1UCL Institute of Neurology; Department of Neuroscience, Physiology and Pharmacology; UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK
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  • ORCID record for Elina A. K. Jacobs
Philip Coen
1UCL Institute of Neurology; Department of Neuroscience, Physiology and Pharmacology; UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK
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Douglas R. Ollerenshaw
3Allen Institute for Brain Science, Seattle WA, USA
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Matthew T. Valley
3Allen Institute for Brain Science, Seattle WA, USA
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Saskia E. J. de Vries
3Allen Institute for Brain Science, Seattle WA, USA
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Marina Garrett
3Allen Institute for Brain Science, Seattle WA, USA
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Jun Zhuang
3Allen Institute for Brain Science, Seattle WA, USA
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Peter A. Groblewski
3Allen Institute for Brain Science, Seattle WA, USA
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Sahar Manavi
3Allen Institute for Brain Science, Seattle WA, USA
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Jesse Miles
3Allen Institute for Brain Science, Seattle WA, USA
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Casey White
3Allen Institute for Brain Science, Seattle WA, USA
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Eric Lee
3Allen Institute for Brain Science, Seattle WA, USA
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Fiona Griffin
3Allen Institute for Brain Science, Seattle WA, USA
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Joshua D Larkin
3Allen Institute for Brain Science, Seattle WA, USA
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Kate Roll
3Allen Institute for Brain Science, Seattle WA, USA
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Sissy Cross
3Allen Institute for Brain Science, Seattle WA, USA
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Thuyanh V. Nguyen
3Allen Institute for Brain Science, Seattle WA, USA
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Rachael Larsen
3Allen Institute for Brain Science, Seattle WA, USA
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Julie Pendergraft
3Allen Institute for Brain Science, Seattle WA, USA
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Tanya Daigle
3Allen Institute for Brain Science, Seattle WA, USA
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Bosiljka Tasic
3Allen Institute for Brain Science, Seattle WA, USA
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Carol L. Thompson
3Allen Institute for Brain Science, Seattle WA, USA
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Jack Waters
3Allen Institute for Brain Science, Seattle WA, USA
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Shawn Olsen
3Allen Institute for Brain Science, Seattle WA, USA
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David J. Margolis
4Rutgers, The State University of New Jersey, Department of Cell Biology and Neuroscience, Piscataway, New Jersey 08854, USA
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Hongkui Zeng
3Allen Institute for Brain Science, Seattle WA, USA
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Michael Hausser
2Wolfson Institute for Biomedical Research; Department of Neuroscience, Physiology and Pharmacology; University College London, London, UK
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Matteo Carandini
1UCL Institute of Neurology; Department of Neuroscience, Physiology and Pharmacology; UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK
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Kenneth D. Harris
1UCL Institute of Neurology; Department of Neuroscience, Physiology and Pharmacology; UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK
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Abstract

Transgenic mouse lines are invaluable tools for neuroscience but as with any technique, care must be taken to ensure that the tool itself does not unduly affect the system under study. Here we report aberrant electrical activity, similar to interictal spikes, and accompanying fluorescence events in some genotypes of transgenic mice expressing GCaMP6 genetically-encoded calcium sensors. These epileptiform events have been observed particularly, but not exclusively, in mice with Emx1-Cre and Ai93 transgenes, across multiple laboratories. The events occur at >0.1 Hz, are very large in amplitude (>1.0 mV local field potentials, >10% df/f widefield imaging signals), and typically cover large regions of cortex. Many properties of neuronal responses and behavior seem normal despite these events, though rare subjects exhibit overt generalized seizures. The underlying mechanisms of this phenomenon remain unclear, but we speculate about possible causes on the basis of diverse observations. We encourage researchers to be aware of these activity patterns while interpreting neuronal recordings from affected mouse lines and when considering which lines to study.

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Posted May 16, 2017.
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Aberrant Cortical Activity In Multiple GCaMP6-Expressing Transgenic Mouse Lines
Nicholas A. Steinmetz, Christina Buetfering, Jerome Lecoq, Christian R. Lee, Andrew J. Peters, Elina A. K. Jacobs, Philip Coen, Douglas R. Ollerenshaw, Matthew T. Valley, Saskia E. J. de Vries, Marina Garrett, Jun Zhuang, Peter A. Groblewski, Sahar Manavi, Jesse Miles, Casey White, Eric Lee, Fiona Griffin, Joshua D Larkin, Kate Roll, Sissy Cross, Thuyanh V. Nguyen, Rachael Larsen, Julie Pendergraft, Tanya Daigle, Bosiljka Tasic, Carol L. Thompson, Jack Waters, Shawn Olsen, David J. Margolis, Hongkui Zeng, Michael Hausser, Matteo Carandini, Kenneth D. Harris
bioRxiv 138511; doi: https://doi.org/10.1101/138511
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Aberrant Cortical Activity In Multiple GCaMP6-Expressing Transgenic Mouse Lines
Nicholas A. Steinmetz, Christina Buetfering, Jerome Lecoq, Christian R. Lee, Andrew J. Peters, Elina A. K. Jacobs, Philip Coen, Douglas R. Ollerenshaw, Matthew T. Valley, Saskia E. J. de Vries, Marina Garrett, Jun Zhuang, Peter A. Groblewski, Sahar Manavi, Jesse Miles, Casey White, Eric Lee, Fiona Griffin, Joshua D Larkin, Kate Roll, Sissy Cross, Thuyanh V. Nguyen, Rachael Larsen, Julie Pendergraft, Tanya Daigle, Bosiljka Tasic, Carol L. Thompson, Jack Waters, Shawn Olsen, David J. Margolis, Hongkui Zeng, Michael Hausser, Matteo Carandini, Kenneth D. Harris
bioRxiv 138511; doi: https://doi.org/10.1101/138511

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