UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Examining the low-voltage fast seizure-onset and its response to optogenetic stimulation in a biophysical network model of the hippocampus

Zhang, L; Ma, Z; Yu, Y; Li, B; Wu, S; Liu, Y; Baier, G; (2023) Examining the low-voltage fast seizure-onset and its response to optogenetic stimulation in a biophysical network model of the hippocampus. Cognitive Neurodynamics 10.1007/s11571-023-09935-1. (In press).

[thumbnail of Zhangetal_Examining_2022.pdf] Text
Zhangetal_Examining_2022.pdf - Other
Access restricted to UCL open access staff until 11 February 2024.

Download (6MB)

Abstract

Low-voltage fast (LVF) seizure-onset is one of the two frequently observed temporal lobe seizure-onset patterns. Depth electroencephalogram profile analysis illustrated that the peak amplitude of LVF onset was deep temporal areas, e.g., hippocampus. However, the specific dynamic transition mechanisms between normal hippocampal rhythmic activity and LVF seizure-onset remain unclear. Recently, the optogenetic approach to gain control over epileptic hyper-excitability both in vitro and in vivo has become a novel noninvasive modulation strategy. Here, we combined biophysical modeling to study LVF dynamics following changes in crucial physiological parameters, and investigated the potential optogenetic intervention mechanism for both excitatory and inhibitory control. In an Ammon’s horn 3 (CA3) biophysical model with light-sensitive protein channelrhodopsin 2 (ChR2), we found that the cooperative effects of excessive extracellular potassium concentration of parvalbumin-positive (PV+) inhibitory interneurons and synaptic links could induce abundant types of discharges of the hippocampus, and lead to transitions from gamma oscillations to LVF seizure-onset. Simulations of optogenetic stimulation revealed that the LVF seizure-onset and morbid fast spiking could not be eliminated by targeting PV+ neurons, whereas the epileptic network was more sensitive to the excitatory control of principal neurons with strong optogenetic currents. We illustrate that in the epileptic hippocampal network, the trajectories of the normal and the seizure state are in close vicinity and optogenetic perturbations therefore may result in transitions. The network model system developed in this study represents a scientific instrument to disclose the underlying principles of LVF, to characterize the effects of optogenetic neuromodulation, and to guide future treatment for specific types of seizures.

Type: Article
Title: Examining the low-voltage fast seizure-onset and its response to optogenetic stimulation in a biophysical network model of the hippocampus
DOI: 10.1007/s11571-023-09935-1
Publisher version: https://doi.org/10.1007/s11571-023-09935-1
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, Low-voltage fast seizure-onset, Hippocampus, Optogenetic stimulation, Parvalbumin-positive inhibitory neurons, Rhythmic oscillation, HIGH-FREQUENCY OSCILLATIONS, EPILEPTIC SEIZURES, HUB NEURONS, GAMMA, SYNCHRONIZATION, CHANNELRHODOPSIN-2, INHIBITION, ACTIVATION, MECHANISMS, DYNAMICS
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10166640
Downloads since deposit
2Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item