NOBLE -- Neural Operator with Biologically-informed Latent Embeddings to Capture Experimental Variability in Biological Neuron Models

Abstract

Characterizing the cellular properties of neurons is fundamental to understanding their function in the brain. In this quest, the generation of bio-realistic models is central towards integrating multimodal cellular data sets and establishing causal relationships. However, current modeling approaches remain constrained by the limited availability and intrinsic variability of experimental neuronal data. The deterministic formalism of bio-realistic models currently precludes accounting for the natural variability observed experimentally. While deep learning is becoming increasingly relevant in this space, it fails to capture the full biophysical complexity of neurons, their nonlinear voltage dynamics, and variability. To address these shortcomings, we introduce NOBLE, a neural operator framework that learns a mapping from a continuous frequency-modulated embedding of interpretable neuron features to the somatic voltage response induced by current injection. Trained on synthetic data generated from bio-realistic neuron models, NOBLE predicts distributions of neural dynamics accounting for the intrinsic experimental variability. Unlike conventional bio-realistic neuron models, interpolating within the embedding space offers models whose dynamics are consistent with experimentally observed responses. NOBLE enables the efficient generation of synthetic neurons that closely resemble experimental data and exhibit trial-to-trial variability, offering a $4200\times$ speedup over the numerical solver. NOBLE is the first scaled-up deep learning framework that validates its generalization with real experimental data. To this end, NOBLE captures fundamental neural properties in a unique and emergent manner that opens the door to a better understanding of cellular composition and computations, neuromorphic architectures, large-scale brain circuits, and general neuroAI applications.