The Virtual Patch Clamp: Imputing C. elegans Membrane Potentials from Calcium Imaging

Andrew Warrington, Arthur Spencer, Frank Wood

TL;DR: We develop a whole-connectome and body simulator for C. elegans and demonstrate joint state-space and parameter inference in the simulator.

Keywords: connectomics, optimisation, state-space estimation, simulation, c. elegans

Abstract: We develop a stochastic whole-brain and body simulator of the nematode roundworm Caenorhabditis elegans (C. elegans) and show that it is sufficiently regularizing to allow imputation of latent membrane potentials from partial calcium fluorescence imaging observations. This is the first attempt we know of to ``complete the circle,'' where an anatomically grounded whole-connectome simulator is used to impute a time-varying ``brain'' state at single-cell fidelity from covariates that are measurable in practice. Using state of the art Bayesian machine learning methods to condition on readily obtainable data, our method paves the way for neuroscientists to recover interpretable connectome-wide state representations, automatically estimate physiologically relevant parameter values from data, and perform simulations investigating intelligent lifeforms in silico.