Computational model of interictal discharges triggered by interneurons

Interictal discharges (IIDs) are abnormal waveforms registered in the periods before or between seizures. IIDs that are initiated by GABAergic interneurons have not been mathematically modeled yet. In the present study, a mathematical model that describes the mechanisms of these discharges is propos...

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Bibliographic Details
Published in:PloS one 2017-10, Vol.12 (10), p.e0185752-e0185752
Main Authors: Chizhov, Anton V, Amakhin, Dmitry V, Zaitsev, Aleksey V
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biology and Life Sciences
Computational neuroscience
Computer applications
Conductance
Cortex (entorhinal)
Depolarization
Discharge
Epilepsy
Firing rate
Gap junctions
Glutamatergic transmission
Glutamic acid receptors (ionotropic)
Hippocampus
Interneurons
Interneurons - physiology
Laboratories
Magnesium
Mathematical models
Medicine and Health Sciences
Models, Biological
N-Methyl-D-aspartic acid receptors
Neurons
Neurosciences
Physical Sciences
Physiology
Populations
Potassium
Pyramidal cells
Rats
Rats, Wistar
Resistance
Seizures
Short term
Synapses
Synaptic depression
Waveforms
α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
γ-Aminobutyric acid
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Summary:Interictal discharges (IIDs) are abnormal waveforms registered in the periods before or between seizures. IIDs that are initiated by GABAergic interneurons have not been mathematically modeled yet. In the present study, a mathematical model that describes the mechanisms of these discharges is proposed. The model is based on the experimental recordings of IIDs in pyramidal neurons of the rat entorhinal cortex and estimations of synaptic conductances during IIDs. IIDs were induced in cortico-hippocampal slices by applying an extracellular solution with 4-aminopyridine, high potassium, and low magnesium concentrations. Two different types of IIDs initiated by interneurons were observed. The first type of IID (IID1) was pure GABAergic. The second type of IID (IID2) was induced by GABAergic excitation and maintained by recurrent interactions of both GABA- and glutamatergic neuronal populations. The model employed the conductance-based refractory density (CBRD) approach, which accurately approximates the firing rate of a population of similar Hodgkin-Huxley-like neurons. The model of coupled excitatory and inhibitory populations includes AMPA, NMDA, and GABA-receptor-mediated synapses and gap junctions. These neurons receive both arbitrary deterministic input and individual colored Gaussian noise. Both types of IIDs were successfully reproduced in the model by setting two different depolarized levels for GABA-mediated current reversal potential. It was revealed that short-term synaptic depression is a crucial factor in ceasing each of the discharges, and it also determines their durations and frequencies.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0185752