Journal of Computational Neuroscience

, Volume 47, Issue 2–3, pp 125–140 | Cite as

Modeling cortical spreading depression induced by the hyperactivity of interneurons

  • Mathieu Desroches
  • Olivier Faugeras
  • Martin KrupaEmail author
  • Massimo Mantegazza


Cortical spreading depression (CSD) is a wave of transient intense neuronal firing leading to a long lasting depolarizing block of neuronal activity. It is a proposed pathological mechanism of migraine with aura. Some forms of migraine are associated with a genetic mutation of the Nav1.1 channel, resulting in its gain of function and implying hyperexcitability of interneurons. This leads to the counterintuitive hypothesis that intense firing of interneurons can cause CSD ignition. To test this hypothesis in silico, we developed a computational model of an E-I pair (a pyramidal cell and an interneuron), in which the coupling between the cells in not just synaptic, but takes into account also the effects of the accumulation of extracellular potassium caused by the activity of the neurons and of the synapses. In the context of this model, we show that the intense firing of the interneuron can lead to CSD. We have investigated the effect of various biophysical parameters on the transition to CSD, including the levels of glutamate or GABA, frequency of the interneuron firing and the efficacy of the KCC2 co-transporter. The key element for CSD ignition in our model was the frequency of interneuron firing and the related accumulation of extracellular potassium, which induced a depolarizing block of the pyramidal cell. This constitutes a new mechanism of CSD ignition.


Cortical spreading depression Migraine Extracellular potassium Interneuron hyperexcitability 


Funding Information

European Union projects DESIRE (grant n. EFP7-602531 to MM) and Investissements d’Avenir-Laboratory of Excellence “Ion Channels Science and Therapeutics” (grant LabEx ICST ANR-11-LABX-0015-01 to MM). ERC Advanced Grant Nervi 227747 (to OF).

Compliance with Ethical Standards

Conflict of interests

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.MathNeuro TeamInria Sophia Antipolis MéditerranéeSophia Antipolis CedexFrance
  2. 2.Université Côte d’AzurNice Cedex 2France
  3. 3.JAD LaboratoryUniversité de Nice Sophia AntipolisNice Cedex 2France
  4. 4.CNRS UMR7275, Institute of Molecular and Cellular Pharmacology (IPMC)LabEx ICSTValbonne-Sophia AntipolisFrance

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