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Spike inference from calcium imaging data acquired with GCaMP8 indicators
Peter Rupprecht1,2, Márton Rózsa3,4, Xusheng Fang5,6
1Laboratory of Neural Circuit Dynamics, Brain Research Institute, University of Zurich, Zurich, Switzerland. rupprecht@hifo.uzh.ch.
Nature Methods
|July 27, 2026
Summary
GCaMP8 calcium indicators offer improved linearity for accurately detecting neuronal activity, including single spikes. This study provides tools and guidelines for interpreting GCaMP8 recordings in neuroscience research.
Area of Science:
- Neuroscience
- Calcium Imaging
- Neuronal Activity Monitoring
Background:
- Calcium imaging is crucial in neuroscience but indirect recording complicates interpretation.
- GCaMP indicators are widely used but their signal linearity impacts data analysis.
- Accurate interpretation of neuronal activity from calcium signals remains a challenge.
Purpose of the Study:
- Evaluate GCaMP8 calcium indicator variants for improved neuronal activity detection.
- Assess the linearity of GCaMP8 variants in inferring neuronal spiking.
- Benchmark spike inference algorithms for GCaMP8 data.
Main Methods:
- In vivo calcium imaging in mouse neocortex using GCaMP8 variants.
- Ground-truth recordings to validate spike detection accuracy.
- Comparative analysis of GCaMP8s, GCaMP8m, GCaMP6, GCaMP7f, and GCaMP8f.
- Benchmarking of spike inference algorithms: CASCADE, OASIS, and MLSpike.
Main Results:
- GCaMP8s and GCaMP8m demonstrate high linearity, accurately detecting single action potentials and high-frequency spiking.
- Linear GCaMP8 variants robustly detect isolated spikes in cortical pyramidal neurons.
- Fast rise time of GCaMP8 indicators facilitates real-time neuronal activity detection.
Conclusions:
- Linearity is key for accurate interpretation of GCaMP8 calcium imaging data.
- GCaMP8s and GCaMP8m offer superior performance for spike detection compared to other variants.
- Optimized algorithms and guidelines enhance the utility of GCaMP8 indicators in neuroscience.

