Energy-based models to describe complex neuronal activities and metabolic constraints

Abstract

In this work, we introduce new phenomenological neuronal models (eLIF and mAdExp) that account for energy supply and demand in the cell as well as the inactivation of spike generation how these interact with subthreshold and spiking dynamics. Including these constraints, the new models reproduce a broad range of biologically-relevant behaviors that are identified to be crucial in many neurological disorders, but were not captured by commonly used phenomenological models. Because of their low dimensionality eLIF and mAdExp open the possibility of future large-scale simulations for more realistic studies of brain circuits involved in neuronal disorders. The new models enable both more accurate modeling and the possibility to study energy-associated disorders over the whole time-course of disease progression instead of only comparing the initially healthy status with the final diseased state. These models, therefore, provide new theoretical and computational methods to assess the opportunities of early diagnostics and the potential of energy-centered approaches to improve therapies. Author summaryNeurons, even "at rest", require a constant supply of energy to function. They cannot sustain high-frequency activity over long periods because of regulatory mechanisms, such as adaptation or sodium channels inactivation, and metabolic limitations. These limitations are especially severe in many neuronal disorders, where energy can become insufficient and make the neuronal response change drastically, leading to increased burstiness, network oscillations, or seizures. Capturing such behaviors and impact of energy constraints on them is an essential prerequisite to study disorders such as Parkinsons disease and epilepsy. However, energy and spiking constraints are not present in any of the standard neuronal models used in computational neuroscience. Here we introduce models that provide a simple and scalable way to account for these features, enabling large-scale theoretical and computational studies of neurological disorders and activity patterns that could not be captured by previously used models. These models provide a way to study energy-associated disorders over the whole time-course of disease progression, and they enable a better assessment of energy-centered approaches to improve therapies.