Widefield Calcium Imaging

We have used "widefield" imaging - covering the entire dorsal surface of the mouse brain - in transgenic mice as they perform a behavioral task. This strategy allows us to simultaneously observe activity across all cortical areas, to study the dynamics and coordination of these areas and their relationship to behavior. Compared to an approach like fMRI, this technique has much higher spatial and temporal resolution, and moreover measures a signal more directly related to neuronal activity (intracellular calcium levels, rather than blood flow).

Our first finding using this technique was, unfortunately, a cautionary tale rather than a scientific outcome. We observed that several of the strains of transgenic mice developed for this purpose exhibited abnormal brain activity, activity similar to that seen in epilepsy. These observations were replicated in several other labs, so we published our findings in order to alert the field to this problem (Steinmetz et al., eNeuro, 2017). This will be an important methodological caveat to bear in mind going forward.

Code that we have written in Matlab for analyzing datasets of this type is available free and open source on github. This includes methods for compressing datasets and efficiently running analyses in the compressed space, methods for correcting imaging contamination due to blood flow, and graphical interfaces for visualizing the data in various convenient ways.

Widefield calcium imaging in transgenic mice. Top, the field of view covering the whole dorsal surface of the mouse brain. Middle, a visual field sign map demarcating the visual areas. Bottom, the response measured to a localized visual stimulus to the right of the mouse.