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Dynamic modeling and closed-loop modulation for absence seizures caused by abnormal glutamate uptake from astrocytes

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Abstract

Absence seizures are not only associated with abnormal interactions in basal gangliacorticothalamic (BGCT) circuits, but are also influenced by glial functions. By introducing extracellular glutamate dynamics associated with neurons and astrocytes, we develop a BGCT model containing the astrocytic function module to simulate seizure phenomena resulting from insufficient glutamate uptake from astrocytes. Differential alterations in the occurrence threshold of spike wave discharges (SWDs) are found by comparing the astrocytic function parameter under different \(\textrm{GABA}_{\textrm{A}}\) or \(\textrm{GABA}_{\textrm{B}}\) inhibition degrees from the reticular nuclei (TRN). Specifically, with enhancement from \(\textrm{GABA}_{\textrm{A}}\) inhibition, thresholds undergo the non-monotonic change, whereas raising \(\textrm{GABA}_{\textrm{B}}\) inhibition will always increase thresholds. Afterwards, we reveal the effects of deep brain stimulation (DBS) frequency and timing on seizure waveform under different pathological degree. Most importantly, a closed-loop strategy based on extracellular glutamate concentration is proposed, which is more on-demand and current-saving than traditional open-loop stimulation. Our theoretical study may provide insights into understanding the astrocytic triggers of absence seizures and further designing regulatory strategies.

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Data availability statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grants Nos. 11932003, 12272092, 12202027, and 12332004).

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Authors and Affiliations

  1. Department of Dynamics and Control, Beihang University, Beijing, 100191, China

    Jinyi Zhao, Ying Yu & Qingyun Wang

  2. College of Information Science and Technology, Donghua University, Shanghai, 201620, China

    Fang Han

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Zhao, J., Yu, Y., Han, F. et al. Dynamic modeling and closed-loop modulation for absence seizures caused by abnormal glutamate uptake from astrocytes. Nonlinear Dyn 112, 3903–3916 (2024). https://doi.org/10.1007/s11071-023-09218-8

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