RT Journal Article
SR Electronic
T1 Precision calcium imaging of dense neural populations via a cell body-targeted calcium indicator
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 773069
DO 10.1101/773069
A1 Or A. Shemesh
A1 Changyang Linghu
A1 Kiryl D. Piatkevich
A1 Daniel Goodwin
A1 Howard J. Gritton
A1 Michael F. Romano
A1 Cody Siciliano
A1 Ruixuan Gao
A1 Chi-Chieh (Jay) Yu
A1 Hua-An Tseng
A1 Seth Bensussen
A1 Sujatha Narayan
A1 Chao-Tsung Yang
A1 Limor Freifeld
A1 Ishan Gupta
A1 Habiba Noamany
A1 Nikita Pak
A1 Young-Gyu Yoon
A1 Jeremy F.P. Ullmann
A1 Burcu Guner-Ataman
A1 Zoe R. Sheinkopf
A1 Won Min Park
A1 Shoh Asano
A1 Amy E. Keating
A1 James S. Trimmer
A1 Jacob Reimer
A1 Andreas Tolias
A1 Kay M. Tye
A1 Xue Han
A1 Misha B. Ahrens
A1 Edward S. Boyden
YR 2019
UL http://biorxiv.org/content/early/2019/09/17/773069.abstract
AB Methods for one-photon fluorescent imaging of calcium dynamics in vivo are popular due to their ability to simultaneously capture the dynamics of hundreds of neurons across large fields of view, at a low equipment complexity and cost. In contrast to two-photon methods, however, one-photon methods suffer from higher levels of crosstalk between cell bodies and the surrounding neuropil, resulting in decreased signal-to-noise and artifactual correlations of neural activity. Here, we address this problem by engineering cell body-targeted variants of the fluorescent calcium indicator GCaMP6f. We screened fusions of GCaMP6f to both natural as well as engineered peptides, and identified fusions that localized GCaMP6f to within approximately 50 microns of the cell body of neurons in live mice and larval zebrafish. One-photon imaging of soma-targeted GCaMP6f in dense neural circuits reported fewer artifactual spikes from neuropil, increased signal-to-noise ratio, and decreased artifactual correlation across neurons. Thus, soma-targeting of fluorescent calcium indicators increases neuronal signal fidelity and may facilitate even greater usage of simple, powerful, one-photon methods of population imaging of neural calcium dynamics.