Higher-order interactions in neuronal function: From genes to ionic currents in biophysical models

Neuronal firing patterns are the consequence of precise variations in neuronal membrane potential, which are themselves shaped by multiple ionic currents. In this study, we use biophysical models, statistical methods, and information theory to explore the interaction between these ionic currents and neuron electrophysiological phenotype. We created numerous electrical models with diverse firing patterns. By analyzing these models, we identified intricate relationships between model parameters and electrical features. Our findings show that neuronal activity is often influenced by multiple biophysical model parameters, in a nonadditive (i.e. synergistic) fashion. When comparing this with single-cell RNAseq data, we found a contrasting structure: gene expression profiles were dominated by redundancy, reflecting differences in regulatory constraints and sampling diversity. This research sheds light on the complex links between biophysical parameters and neuronal phenotypes.