Cell to network computational model of the epileptic human hippocampus suggests specific roles of network and channel dysfunctions in the ictal and interictal oscillations

Abstract

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 microand 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.

Bridging model and experiment in systems neuroscience with Cleo: the Closed-Loop, Electrophysiology, and Optophysiology simulation testbed

“…To demonstrate Cleo’s capabilities to simulate optimal feedback control and approximate LFP, we interfaced Cleo with an anatomically informed model of the hippocampus previously reported [85, 86]. When a sustained external current is delivered to the entorhinal cortex of this model to simulate the slow waves of non-REM sleep, the model produces a sharp wave-ripple (SWR)-like pattern of LFPs [87], as approximated by the reference weighted sum method of [75].…”

“…An example application of Cleo to the anatomical hippocampus model by Aussel et al . [85, 86]. (A) A 2.5 mm-thick slice of the 15 mm-tall model is shown.…”

A dynamical computational model of theta generation in hippocampal circuits to study theta-gamma oscillations during neurostimulation

“…The following sections describe in detail how individual neurons and synapses were modeled, and are adapted from the original work by Aussel and colleagues ( Aussel et al, 2018 ). Neurons were modeled as conductance-based single compartments, following the Hodgkin-Huxley formalism ( Hodgkin and Huxley, 1952 ), in line with previous work ( Aussel et al, 2022, 2018 ). The temporal evolution of the membrane potential of each neuron is described by a differential equation whose general form reads: I L denotes the leakage current.…”

A dynamical computational model of theta generation in hippocampal circuits to study theta-gamma oscillations during neurostimulation

“…The following sections describe in detail how individual neurons and synapses were modeled, and are adapted from the original work by Aussel and colleagues (Aussel et al, 2018). Neurons were modeled as conductance-based single compartments, following the Hodgkin-Huxley formalism (Hodgkin and Huxley, 1952), in line with previous work (Aussel et al, 2022(Aussel et al, , 2018. The temporal evolution of the membrane potential of each neuron is described by a differential equation whose general form reads: I L denotes the leakage current.…”