DOI: 10.1101/479055Nov 29, 2018Paper

Accurate action potential inference from a calcium sensor protein through biophysical modeling

BioRxiv : the Preprint Server for Biology
David S GreenbergJason N D Kerr

Abstract

Multiphoton imaging of genetically encoded calcium indicators is routinely used to report activity from populations of spatially resolved neurons in vivo. However, since the relationship between fluorescence and action potentials (APs) is nonlinear and varies over neurons, quantitatively inferring AP discharge is problematic. To address this we developed a biophysical model of calcium binding kinetics for the indicator GCaMP6s that accurately describes AP-evoked fluorescence changes in vivo. The model's physical interpretation allowed the same parameters to describe GCaMP6s binding kinetics for both in vitro binding assays and in vivo imaging. Using this model, we developed an algorithm to infer APs from fluorescence and measured its accuracy with cell-attached electrical recordings. This approach consistently inferred more accurate AP counts and times than alternative methods for firing rates from 0 to >20 Hz, while requiring less training data. These results demonstrate the utility of quantitative, biophysically grounded models for complex biological data.

Related Concepts

Calcium-Binding Proteins
Cell Adhesion
Diagnostic Imaging
Indicators
Neurons
Patient Discharge
Acanthamoeba polyphaga
calcium indicator
Binding (Molecular Function)
Mle protein, Drosophila

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