High-performance GFP-based calcium indicators for imaging activity in neuronal populations and microcompartments
Hod DanaiD, Yi SuniD, Boaz MohariD, Brad K. HulseiD, Jeremy P. HassemaniD, Getahun Tsegaye, Arthur TsangiD, Allan M. WongiD, Ronak H. PateliD, John J MackliniD, Yang CheniD, Arthur KonnerthiD, Vivek JayaramaniD, Loren L. LoogeriD, Eric R. SchreiteriD, Karel SvobodaiD, Douglas S. KimiD
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 jGCaMP7 sensors provide improved detection of individual spikes (jGCaMP7s,f), imaging in neurites and neuropil (jGCaMP7b), and tracking large populations of neurons using 2-photon (jGCaMP7s,f) or wide-field (jGCaMP7c) imaging.
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Abstract summary
Claude Opus 5.5 · xhigh effort · 18 Oct 2026 · from the abstract · CC BY-NC-ND 4.0
Structure-guided mutagenesis of GCaMP6 plus neuron-based screening yields a jGCaMP7 family, each variant tuned to a different regime: single spikes, neurites and neuropil, or population imaging.
Calcium imaging is bounded by the biophysics of the available genetically encoded calcium indicators (GECIs) - affinity, signal-to-noise, rise and decay kinetics, dynamic range - while the same class of sensor is asked to serve two different uses, tracking large populations of cell bodies and following subcellular compartments such as axons, dendrites and synapses. The authors engineer a set of variants from GCaMP6, each optimized for one of these in vivo imaging modes.
Key results
ClaimedTwo variants, jGCaMP7s and jGCaMP7f, are reported to give improved detection of individual action potentials.
Stated as improved spike detection; the abstract gives no detection rate, signal-to-noise figure, kinetics or explicit baseline comparison. · Abstract
ClaimedA separate variant, jGCaMP7b, is aimed at imaging thin processes and neuropil rather than cell bodies.
Named in the abstract as the variant for neurites and neuropil; no brightness, dynamic range or compartment-level measurement is reported. · Abstract
ClaimedPopulation recording is split across variants by microscope: jGCaMP7s and jGCaMP7f for two-photon imaging, jGCaMP7c for wide-field imaging.
Assignment of variants to imaging modality is asserted in the abstract, without cell counts, field sizes or comparative performance numbers. · Abstract
Methods, data and reproducibility
The green fluorescent protein-based indicator GCaMP6 was altered by structure-guided mutagenesis, and the resulting variants were screened in neurons and selected for different in vivo imaging regimes.
- Methods & tools
- GCaMP6, jGCaMP7s, jGCaMP7f, jGCaMP7b, jGCaMP7c, two-photon imaging, wide-field imaging
Limitations (2)
- The sensor properties the authors name as limiting - affinity, signal-to-noise, rise and decay kinetics, dynamic range - are never quantified in the available text, so the variants cannot be compared with existing GECIs. · noted in this summary
- No species, preparation or brain region is named for the in vivo imaging, so the conditions under which each variant was selected are unknown here. · noted in this summary
Who should read:Read this if you do calcium imaging and need to pick a GECI matched to single-spike detection, neurite and neuropil signals, or large-population recording.
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