Fast reconstruction of degenerate populations of conductance-based neuron models from spike times using deep learning
Abstract
Inferring the biophysical parameters of conductance-based models (CBMs) from experimentally accessible recordings remains a central challenge in computational neuroscience. Spike times are the most widely available data, yet they reveal little about which combinations of ionic conductances generate the observed activity. This inverse problem is further complicated by neuronal degeneracy, where multiple distinct sets of conductances yield similar spiking patterns. We introduce a method that addresses this challenge by combining deep learning with Dynamic Input Conductances (DICs), a theoretical framework that reduces complex CBMs to three interpretable aggregated conductances that separate according to timescales. DIC values directly relate to excitability and firing patterns. Our approach first maps spike times directly to DIC values at threshold using a lightweight neural network that learns a low-dimensional representation of neuronal activity. The predicted DIC values are then used to generate degenerate CBM populations via an improved state-of-the-art algorithm. Applied to two neuronal models, this algorithmic pipeline reconstructs spiking, bursting, and irregular regimes with high accuracy and robustness to variability, including spike trains generated by Poisson processes. It produces diverse degenerate populations within milliseconds on standard hardware, enabling scalable and efficient inference from spike recordings alone. Beyond methodological advances, we provide an open-source software package with a graphical interface that allows experimentalists to generate and explore CBM populations directly from spike trains without requiring programming expertise.