Aberrant Cortical Activity In Multiple GCaMP6-Expressing Transgenic Mouse Lines

Steinmetz, N. A.; Buetfering, C.; Lecoq, J.; Lee, C. R.; Peters, A. J.; Jacobs, E. A. K.; Coen, P.; Ollerenshaw, D. R.; Valley, M. T.; de Vries, S. E. J.; Garrett, M.; Zhuang, J.; Groblewski, P. A.; Manavi, S.; Miles, J.; White, C.; Lee, E.; Griffin, F.; Larkin, J. D.; Roll, K.; Cross, S.; Nguyen, T. V.; Larsen, R.; Pendergraft, J.; Daigle, T.; Tasic, B.; Thompson, C. L.; Waters, J.; Olsen, S.; Margolis, D. J.; Zeng, H.; Hausser, M.; Carandini, M.; Harris, K. D.

doi:10.1101/138511

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bioRxiv · 10.1101/138511

Aberrant Cortical Activity In Multiple GCaMP6-Expressing Transgenic Mouse Lines

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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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Steinmetz, N. A., Buetfering, C., Lecoq, J., Lee, C. R., Peters, A. J., Jacobs, E. A. K., Coen, P., Ollerenshaw, D. R., Valley, M. T., de Vries, S. E. J., Garrett, M., Zhuang, J., Groblewski, P. A., Manavi, S., Miles, J., White, C., Lee, E., Griffin, F., Larkin, J. D., Roll, K., Cross, S., Nguyen, T. V., Larsen, R., Pendergraft, J., Daigle, T., Tasic, B., Thompson, C. L., Waters, J., Olsen, S., Margolis, D. J., Zeng, H., Hausser, M., Carandini, M., Harris, K. D.. 2017-05-16. Aberrant Cortical Activity In Multiple GCaMP6-Expressing Transgenic Mouse Lines. https://doi.org/10.1101/138511

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