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 RollSissy 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

Research output: Contribution to journalArticlepeer-review

169 Scopus citations

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, 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, although 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.

Original languageEnglish (US)
Article numbere0207-17.2017
JournaleNeuro
Volume4
Issue number5
DOIs
StatePublished - Sep 1 2017

All Science Journal Classification (ASJC) codes

  • General Neuroscience

Keywords

  • Cortex
  • Epilepsy
  • GCaMP
  • Transgenic

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