Cell to network computational model of the epileptic human hippocampus suggests specific roles of network and channel dysfunctions in the ictal and interictal oscillations
J Comput Neurosci. 2022-08-16; 50(4): 519-535
DOI: 10.1007/s10827-022-00829-5
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Aussel A(1)(2), Ranta R(3), Aron O(3)(4), Colnat-Coulbois S(3)(4), Maillard L(3)(4), Buhry L(5).
Author information:
(1)Laboratoire Lorrain de Recherche en Informatique et ses applications (LORIA
UMR 7503), University of Lorraine, 54506, Nancy, France. .
(2)Centre de Recherche en Automatique de Nancy, University of Lorraine,
CRAN-CNRS UMR 7039, Nancy, France. .
(3)Centre de Recherche en Automatique de Nancy, University of Lorraine,
CRAN-CNRS UMR 7039, Nancy, France.
(4)Department of Neurology, CHU de Nancy, Nancy, France.
(5)Laboratoire Lorrain de Recherche en Informatique et ses applications (LORIA
UMR 7503), University of Lorraine, 54506, Nancy, France.
The mechanisms underlying the generation of hippocampal epileptic seizures and
interictal events and their interactions with the sleep-wake cycle are not yet
fully understood. Indeed, medial temporal lobe epilepsy is associated with
hippocampal abnormalities both at the neuronal (channelopathies, impaired
potassium and chloride dynamics) and network level (neuronal and axonal loss,
mossy fiber sprouting), with more frequent seizures during wakefulness compared
with slow-wave sleep. In this article, starting from our previous computational
modeling work of the hippocampal formation based on realistic topology and
synaptic connectivity, we study the role of micro- and mesoscale pathological
conditions of the epileptic hippocampus in the generation and maintenance of
seizure-like theta and interictal oscillations. We show, through the simulations
of hippocampal activity during slow-wave sleep and wakefulness that: (i) both
mossy fiber sprouting and sclerosis account for seizure-like theta activity,
(ii) but they have antagonist effects (seizure-like activity occurrence
increases with sprouting but decreases with sclerosis), (iii) though impaired
potassium and chloride dynamics have little influence on the generation of
seizure-like activity, they do play a role on the generation of interictal
patterns, and (iv) seizure-like activity and fast ripples are more likely to
occur during wakefulness and interictal spikes during sleep.
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