RT Journal Article SR Electronic T1 Aberrant Cortical Activity in Multiple GCaMP6-Expressing Transgenic Mouse Lines JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0207-17.2017 DO 10.1523/ENEURO.0207-17.2017 A1 Nicholas A. Steinmetz A1 Christina Buetfering A1 Jerome Lecoq A1 Christian R. Lee A1 Andrew J. Peters A1 Elina A. K. Jacobs A1 Philip Coen A1 Douglas R. Ollerenshaw A1 Matthew T. Valley A1 Saskia E. J. de Vries A1 Marina Garrett A1 Jun Zhuang A1 Peter A. Groblewski A1 Sahar Manavi A1 Jesse Miles A1 Casey White A1 Eric Lee A1 Fiona Griffin A1 Joshua D Larkin A1 Kate Roll A1 Sissy Cross A1 Thuyanh V. Nguyen A1 Rachael Larsen A1 Julie Pendergraft A1 Tanya Daigle A1 Bosiljka Tasic A1 Carol L. Thompson A1 Jack Waters A1 Shawn Olsen A1 David J. Margolis A1 Hongkui Zeng A1 Michael Hausser A1 Matteo Carandini A1 Kenneth D. Harris YR 2017 UL http://www.eneuro.org/content/early/2017/09/04/ENEURO.0207-17.2017.abstract AB 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, of either sex, 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.Significance Statement Genetically-encoded calcium sensors have revolutionized neuroscience by providing a powerful way to measure neural activity with optical imaging. Transgenic mice that express these indicators have proved a particularly useful technology for their stability, ease of use, and breadth of expression. However, here we report that some of these mouse lines have major abnormalities in their brain activity, including large, broad events resembling epileptic activity. We confirmed these abnormalities across multiple laboratories and we provide methods to detect them. This finding is an important point of caution for researchers using genetically-encoded calcium indicators to study neural activity.