A computational model of motor neuron degeneration

Neuron. 2014 Aug 20;83(4):975-88. doi: 10.1016/j.neuron.2014.07.001. Epub 2014 Jul 31.


To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials / physiology*
  • Adenosine Triphosphate / metabolism
  • Calcium / metabolism
  • Energy Metabolism*
  • Homeostasis / physiology
  • Models, Neurological*
  • Motor Neurons / pathology*
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / pathology*
  • Nerve Degeneration / physiopathology*
  • Potassium / metabolism
  • Sodium / metabolism


  • Adenosine Triphosphate
  • Sodium
  • Potassium
  • Calcium