Simple models including energy and spike constraints reproduce complex activity patterns and metabolic disruptions

PLoS Comput Biol. 2020 Dec 21;16(12):e1008503. doi: 10.1371/journal.pcbi.1008503. eCollection 2020 Dec.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Brain / metabolism
  • Brain / physiology
  • Energy Metabolism*
  • Humans
  • Models, Neurological*
  • Nerve Net
  • Parkinson Disease / metabolism
  • Parkinson Disease / physiopathology
  • Seizures / metabolism
  • Seizures / physiopathology
  • Sodium-Potassium-Exchanging ATPase / metabolism

Substances

  • Sodium-Potassium-Exchanging ATPase

Grants and funding

TF was awarded a Humboldt Research Fellowship for Postdoctoral Researchers and AL was awarded a a Sofja Kovalevskaja Award from the Alexander von Humboldt Foundation: https://www.humboldt-foundation.de. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.