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 Ullmann; Burcu 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

doi:10.1016/j.neuron.2020.05.029

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

Neuron. 2020 Aug 5;107(3):470-486.e11. doi: 10.1016/j.neuron.2020.05.029. Epub 2020 Jun 26.

Authors

Or A Shemesh¹, Changyang Linghu², Kiryl D Piatkevich³, Daniel Goodwin⁴, Orhan Tunc Celiker⁵, Howard J Gritton⁶, Michael F Romano⁶, Ruixuan Gao⁷, Chih-Chieh Jay Yu⁸, Hua-An Tseng⁶, Seth Bensussen⁶, Sujatha Narayan⁹, Chao-Tsung Yang⁹, Limor Freifeld¹⁰, Cody A Siciliano¹¹, Ishan Gupta¹², Joyce Wang¹³, Nikita Pak¹⁴, Young-Gyu Yoon¹⁵, Jeremy F P Ullmann¹⁶, Burcu Guner-Ataman¹⁷, Habiba Noamany¹³, Zoe R Sheinkopf¹⁸, Won Min Park¹⁹, Shoh Asano²⁰, Amy E Keating²¹, James S Trimmer²², Jacob Reimer²³, Andreas S Tolias²⁴, Mark F Bear¹³, Kay M Tye²⁵, Xue Han⁶, Misha B Ahrens⁹, Edward S Boyden²⁶

Affiliations

¹ The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA; Department of Neurobiology and Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
² The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA; Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA, USA.
³ The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA; School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province, China.
⁴ The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA.
⁵ MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA; Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA, USA.
⁶ Boston University, Department of Biomedical Engineering, Boston, MA 02215, USA.
⁷ The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA.
⁸ The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA.
⁹ Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
¹⁰ The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA; Faculty of Biomedical Engineering, Technion, Haifa, Israel.
¹¹ Vanderbilt Center for Addiction Research, Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
¹² The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA.
¹³ The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA.
¹⁴ The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA; Department of Mechanical Engineering, MIT, Cambridge, MA, USA.
¹⁵ The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA; Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA, USA; School of Electrical Engineering, KAIST Institute for Health Science and Technology, Daejeon, Republic of Korea.
¹⁶ Epilepsy Genetics Program, Department of Neurology, Boston Children's Hospital & Harvard Medical School, Boston, MA, USA.
¹⁷ The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
¹⁸ The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
¹⁹ Department of Biology, MIT, Cambridge, MA, USA.
²⁰ Internal Medicine Research Unit, Pfizer, Cambridge, MA, USA.
²¹ Department of Biological Engineering, MIT, Cambridge, MA, USA; Department of Biology, MIT, Cambridge, MA, USA; Koch Institute, MIT, Cambridge, MA 02139, USA.
²² Department of Physiology and Membrane Biology, University of California, Davis School of Medicine, Davis, CA, USA.
²³ Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA; Center for Neuroscience and AI, Baylor College of Medicine, Houston, TX, USA.
²⁴ Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA; Center for Neuroscience and AI, Baylor College of Medicine, Houston, TX, USA; Department of Electrical and Computer Engineering, Rice University, Houston, TX, USA.
²⁵ The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA; Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
²⁶ The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA; Koch Institute, MIT, Cambridge, MA 02139, USA. Electronic address: edboyden@mit.edu.

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.

Keywords: GCaMP6; GCaMP7; calcium imaging; correlation; crosstalk; in vivo imaging; microscopy; neuropil contamination; soma-targeting; two-photon microscopy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Artifacts
Brain / diagnostic imaging*
Brain / metabolism
Brain / pathology
Calcium / metabolism*
Calcium-Binding Proteins
Cell Body / metabolism
Cell Body / pathology*
Green Fluorescent Proteins
Mice
Neurons / metabolism
Neurons / pathology*
Neuropil
Optical Imaging / methods*
Zebrafish

Substances

Calcium-Binding Proteins
Green Fluorescent Proteins
Calcium

Abstract

Publication types

MeSH terms

Substances

Grants and funding