Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator

Or A. Shemesh, Changyang Linghu, Kiryl D. Piatkevich, Daniel Goodwin, Orhan Tunc Celiker, Howard J. Gritton, Michael F. Romano, Ruixuan Gao, Chih Chieh (Jay) Yu, Hua An Tseng, Seth Bensussen, Sujatha Narayan, Chao Tsung Yang, Limor Freifeld, Cody A. Siciliano, Ishan Gupta, Joyce Wang, Nikita Pak, Young Gyu Yoon, Jeremy F.P. UllmannBurcu Guner-Ataman, Habiba Noamany, Zoe R. Sheinkopf, Won Min Park, Shoh Asano, Amy E. Keating, James S. Trimmer, Jacob Reimer, Andreas S. Tolias, Mark F. Bear, Kay M. Tye, Xue Han, Misha B. Ahrens, Edward S. Boyden

Research output: Contribution to journalArticlepeer-review

Abstract

Methods for one-photon fluorescent imaging of calcium dynamics can capture the activity 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 from neuropil, resulting in a decreased signal-to-noise ratio and artifactual correlations of neural activity. We address this problem by engineering cell-body-targeted variants of the fluorescent calcium indicators GCaMP6f and GCaMP7f. We screened fusions of GCaMP to natural, as well as artificial, peptides and identified fusions that localized GCaMP to within 50 μm of the cell body of neurons in mice and larval zebrafish. One-photon imaging of soma-targeted GCaMP in dense neural circuits reported fewer artifactual spikes from neuropil, an increased signal-to-noise ratio, and decreased artifactual correlation across neurons. Thus, soma-targeting of fluorescent calcium indicators facilitates usage of simple, powerful, one-photon methods for imaging neural calcium dynamics.

Original languageEnglish
Pages (from-to)470-486.e11
JournalNeuron
Volume107
Issue number3
DOIs
StatePublished - 5 Aug 2020

Keywords

  • GCaMP6
  • GCaMP7
  • calcium imaging
  • correlation
  • crosstalk
  • in vivo imaging
  • microscopy
  • neuropil contamination
  • soma-targeting
  • two-photon microscopy

All Science Journal Classification (ASJC) codes

  • General Environmental Science
  • Industrial and Manufacturing Engineering
  • Renewable Energy, Sustainability and the Environment
  • Strategy and Management

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