AI Article Synopsis
- The influence of GABAergic neurotransmission on the development of epilepsy is complex, particularly because the GABAa neurotransmitter can switch from inhibitory to excitatory effects depending on chloride levels inside neurons.
- A computational model was created to simulate the dentate gyrus, incorporating three types of neurons and using specific interconnection rules, which successfully reproduced seizure-like activity (ictal discharges).
- The study's findings suggest that abnormal sprouting of mossy fibers, driven by the excitatory effects of GABAa, causes alterations in neuronal connectivity that may lead to increased seizure activity.
Article Abstract
The role of GABAergic neurotransmission on epileptogenesis has been the subject of speculation according to different approaches. However, it is a very complex task to specifically consider the action of the GABAa neurotransmitter, which, in its dependence on the intracellular level of Cl, can change its effect from inhibitory to excitatory. We have developed a computational model that represents the dentate gyrus and is composed of three different populations of neurons (granule cells, interneurons and mossy cells) that are mutually interconnected. The interconnections of the neurons were based on compensation theory with Hebbian and anti-Hebbian rules. The model also incorporates non-synaptic mechanisms to control the ionic homeostasis and was able to reproduce ictal discharges. The goal of the work was to investigate the hypothesis that the observed aberrant sprouting is promoted by GABAa excitatory action. Conjointly with the abnormal sprouting of the mossy fibres, the simulations show a reduction of the mossy cells connections in the network and an increased inhibition of the interneurons as a response of the neuronal network to control the activity. This finding contributes to increasing the changes in the connectivity of the neuronal circuitry and to increasing the epileptiform activity occurrences.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843660 | PMC |
| http://dx.doi.org/10.1038/s41598-018-22581-6 | DOI Listing |
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