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).
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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 |
| Open access status: | An open access version is available from UCL Discovery |
| 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 |
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