Capturing Membrane Dynamics and Spike Timing of Human Neurons at Scale using Neural Operators

Abstract

Characterizing the properties of neuronal cell types is central to understanding brain function. Yet, biophysically realistic neuron models remain difficult to scale to large populations while preserving the richness of cellular dynamics and within-cell-type variability. We present a cell-type-specific neural-operator framework for scalable neuronal population modeling. Rather than training separate surrogate models for individual neurons, the proposed framework learns a shared operator across multiple modeled neurons from the same cell type, conditioned on biologically interpretable electrophysiological features. Relative to the original single-neuron \texttt{NOBLE} setting, learning across heterogeneous neurons requires a richer electrophysiological conditioning representation and a training objective designed to preserve diverse spiking dynamics. This enables efficient generation of large ensembles of somatic voltage responses while preserving variability across cells and model configurations. We evaluate the approach using membrane dynamics metrics, action potential waveform metrics, spike timing accuracy, input-output firing relationships, and electrophysiological feature distributions. Our framework reproduces subthreshold membrane dynamics, spike waveforms, and firing-rate responses across major cortical inhibitory neuron types, while accurately preserving spike timing despite the sensitivity of threshold-crossing dynamics. The predicted electrophysiological feature distributions show strong agreement with detailed simulator outputs and human experimental recordings, including high explained variability in properties such as inter-spike intervals, firing frequency, action-potential shape, and post-spike recovery.