Neurons with identical firing patterns can fail differently under stress

Two neurons can look indistinguishable on a recording trace yet be built very differently underneath. A new computational study in PLOS Computational Biology examines this phenomenon, known as degeneracy, at the level of neuronal dynamics and finds that configurations producing identical activity patterns are not interchangeable when conditions change. The work, by Gianmarco Cafaro, Christophe Bernard, Meysam Hashemi and Damien Depannemaecker, shows that structurally distinct parameter sets can follow the same bifurcation sequences while responding very differently to external perturbations.

Degeneracy is the capacity of structurally distinct systems to achieve similar functions, a property the authors describe as fundamental to living organisms because it enables adaptability and resilience. Neurons are a prime example: they can maintain stable activity patterns despite substantial variability in ion channel expression, meaning different intrinsic configurations can produce equivalent electrophysiological behaviors. Previous studies had established that neuronal activity emerges from the interaction between intrinsic membrane properties and ionic concentration dynamics. What remained poorly understood, the researchers note, is how degeneracy is organized within the dynamical landscape of a neuron, and how different degenerate configurations respond to external perturbations.

To address this, the team used a minimal neuron model with three variable conductances, systematically exploring how variations in extracellular potassium concentration, representing physiological and pathological conditions, reshape neuronal dynamics. The central result is that distinct conductance configurations occupy structured regions of parameter space that support the same bifurcation pathways, leading to equivalent activity regimes such as bursting, seizure-like activity and depolarization block. In other words, very different combinations of channel conductances could reproduce the same sequence of dynamical states as conditions shifted.

Functional equivalence, however, turned out to be only half the story. When the authors tested how these degenerate configurations responded to extracellular perturbations, they found different sensitivities across configurations. The study’s key conclusion is that functional equivalence under fixed conditions does not imply equivalent robustness.

To make this comparison quantitative, the researchers introduce resilience as a measure of the threshold at which a given conductance configuration transitions into a specific activity regime under external ionic changes. This turns resilience from a vague descriptor into a computable quantity: for each configuration, one can determine how far extracellular potassium must move before the system enters a regime such as depolarization block. Two configurations sharing the same bifurcation sequence can therefore carry different resilience thresholds.

The authors argue that their results demonstrate degeneracy extends beyond the coexistence of multiple solutions: degenerate configurations form structured landscapes with distinct trajectories under environmental modulation. The framework offers a quantitative approach to investigating how intrinsic variability influences neuronal vulnerability and resilience across different dynamical states. As a minimal-model study, it establishes a conceptual and computational map rather than a direct measurement in living tissue, but it gives researchers a concrete tool for dissecting how degeneracy shapes susceptibility to seizure-like states and depolarization block.

Subject of Research: How distinct neuronal parameter sets generate equivalent bifurcation sequences yet differ in resilience to ionic perturbations

Article Title: Degeneracy in neuronal bifurcation landscapes: Equivalent bifurcation sequences across distinct parameter sets

Article References: Cafaro, G., Bernard, C., Hashemi, M., & Depannemaecker, D. (2026). Degeneracy in neuronal bifurcation landscapes: Equivalent bifurcation sequences across distinct parameter sets. PLOS Computational Biology, 22(10), e1014893. https://doi.org/10.1371/journal.pcbi.1014893

Image Credits: AI Generated

DOI: 10.1371/journal.pcbi.1014893

Keywords: neuronal degeneracy, bifurcation, ion channels, extracellular potassium, resilience, depolarization block, seizure-like activity, bursting, computational neuroscience, dynamical systems, Degeneracy, neuronal