Format

Send to

Choose Destination
J Comput Neurosci. 2019 Oct 17. doi: 10.1007/s10827-019-00730-8. [Epub ahead of print]

Modeling cortical spreading depression induced by the hyperactivity of interneurons.

Author information

1
MathNeuro Team, Inria Sophia Antipolis Méditerranée, 06902, Sophia Antipolis Cedex, France.
2
Université Côte d'Azur, 06108, Nice Cedex 2, France.
3
MathNeuro Team, Inria Sophia Antipolis Méditerranée, 06902, Sophia Antipolis Cedex, France. martin.krupa@unice.fr.
4
Université Côte d'Azur, 06108, Nice Cedex 2, France. martin.krupa@unice.fr.
5
JAD Laboratory, Université de Nice Sophia Antipolis, 06108, Nice Cedex 2, France. martin.krupa@unice.fr.
6
CNRS UMR7275, Institute of Molecular and Cellular Pharmacology (IPMC), LabEx ICST, 06560, Valbonne-Sophia Antipolis, France.

Abstract

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.

KEYWORDS:

Cortical spreading depression; Extracellular potassium; Interneuron hyperexcitability; Migraine

PMID:
31620945
DOI:
10.1007/s10827-019-00730-8

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center