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.
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This work was supported by the National Key Research and Development Program of China (Grant Nos. 2021YFA1000200 and 2021YFA1000202), the National Natural Science Foundation of China (Grant Nos. 12102014 and 11932003), the China Postdoctoral Science Foundation (Grant No. 2021M700307), and the Beijing Postdoctoral Research Foundation (Grant No. 2021-ZZ-058).
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YL and GB contributed equally to this work. LZ, ZM, YY, BL, SW, YL and GB designed ideas, performed algorithm implementation, analyzed the data, and wrote the paper. All authors contributed to the article.
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Zhang, L., Ma, Z., Yu, Y. et al. Examining the low-voltage fast seizure-onset and its response to optogenetic stimulation in a biophysical network model of the hippocampus. Cogn Neurodyn 18, 265–282 (2024). https://doi.org/10.1007/s11571-023-09935-1
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DOI: https://doi.org/10.1007/s11571-023-09935-1