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Nat Methods. 2019 Jul;16(7):649-657. doi: 10.1038/s41592-019-0435-6. Epub 2019 Jun 17.

High-performance calcium sensors for imaging activity in neuronal populations and microcompartments.

Author information

1
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
2
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
3
School of Life Sciences, Westlake University, Hangzhou, China.
4
Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA.
5
Institute of Neuroscience and SyNergy Cluster, Technical University of Munich, Munich, Germany.
6
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. jayaramanv@janelia.hhmi.org.
7
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. loogerl@janelia.hhmi.org.
8
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. svobodak@janelia.hhmi.org.
9
National Institute of Mental Health, Rockville, MD, USA.

Abstract

Calcium imaging with genetically encoded calcium indicators (GECIs) is routinely used to measure neural activity in intact nervous systems. GECIs are frequently used in one of two different modes: to track activity in large populations of neuronal cell bodies, or to follow dynamics in subcellular compartments such as axons, dendrites and individual synaptic compartments. Despite major advances, calcium imaging is still limited by the biophysical properties of existing GECIs, including affinity, signal-to-noise ratio, rise and decay kinetics and dynamic range. Using structure-guided mutagenesis and neuron-based screening, we optimized the green fluorescent protein-based GECI GCaMP6 for different modes of in vivo imaging. The resulting jGCaMP7 sensors provide improved detection of individual spikes (jGCaMP7s,f), imaging in neurites and neuropil (jGCaMP7b), and may allow tracking larger populations of neurons using two-photon (jGCaMP7s,f) or wide-field (jGCaMP7c) imaging.

PMID:
31209382
DOI:
10.1038/s41592-019-0435-6
[Indexed for MEDLINE]

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