Targeted optogenetic stimulation of the thalamic reticular nucleus: A novel strategy for modulating epileptiform discharges

doi:10.1088/1674-1056/ae516f

摘要/Abstract

摘要： The distinct advantage of optogenetic stimulation in precise neuromodulation enables us to dissect the intrinsic mechanisms by which such stimulation of the thalamic reticular nucleus (RE) suppresses epileptic seizures. Since irradiance ($I_{\rm rr}$) is a key factor affecting optogenetic stimulation, we first explore the effect of $I_{\rm rr}$ on epileptic seizures. The results indicate that increasing $I_{\rm rr}$ can suppress the seizures and alter the system's bifurcation structure. The numbers of Hopf bifurcations and saddle-node bifurcations of limit cycles decrease as $I_{\rm rr}$ increases, and the saddle-node bifurcation of the fixed point is a key factor driving the abrupt transition of the system from a high-saturation discharge state to a low-saturation discharge state. Subsequently, we apply optogenetic stimulation in square-wave and Gaussian pulse forms to assess the impacts of three core parameters (pulse width $w_{\rm s}$, pulse frequency $f$, and $I_{\rm rr}$) on epileptic discharge states. Our numerical simulation results reveal that square-wave pulsed optogenetic stimulation effectively suppresses seizure activity when the pulse width is increased to $15$ ms ($f=40$ Hz, $I_{\rm rr}=0.3$ mW/mm$^2$), the pulse frequency to $100$ Hz ($w_{\rm s}=5$ ms, $I_{\rm rr}=0.3$ mW/mm$^2$), and the irradiance to $0.8 $ mW/mm$^2$ ($w_{\rm s}=5$ ms, $f=40$ Hz), respectively. In contrast, using the same analytical method, we find that Gaussian pulsed stimulation requires elevating the respective parameters (pulse width, frequency, irradiance) to $30$ ms, $250 $ Hz, and $1.9 $ mW/mm$^2$ for the effective suppression of seizure activity. Therefore, square-wave pulses require a smaller parameter threshold to achieve the effect of inhibiting epileptic seizures. From a physiological perspective, square-wave pulsed optogenetic stimulation is thus more suitable as a potential candidate for clinical trials.

关键词: optogenetic stimulation, square-wave pulse, Gaussian pulse, bifurcation analysis

Abstract: The distinct advantage of optogenetic stimulation in precise neuromodulation enables us to dissect the intrinsic mechanisms by which such stimulation of the thalamic reticular nucleus (RE) suppresses epileptic seizures. Since irradiance ($I_{\rm rr}$) is a key factor affecting optogenetic stimulation, we first explore the effect of $I_{\rm rr}$ on epileptic seizures. The results indicate that increasing $I_{\rm rr}$ can suppress the seizures and alter the system's bifurcation structure. The numbers of Hopf bifurcations and saddle-node bifurcations of limit cycles decrease as $I_{\rm rr}$ increases, and the saddle-node bifurcation of the fixed point is a key factor driving the abrupt transition of the system from a high-saturation discharge state to a low-saturation discharge state. Subsequently, we apply optogenetic stimulation in square-wave and Gaussian pulse forms to assess the impacts of three core parameters (pulse width $w_{\rm s}$, pulse frequency $f$, and $I_{\rm rr}$) on epileptic discharge states. Our numerical simulation results reveal that square-wave pulsed optogenetic stimulation effectively suppresses seizure activity when the pulse width is increased to $15$ ms ($f=40$ Hz, $I_{\rm rr}=0.3$ mW/mm$^2$), the pulse frequency to $100$ Hz ($w_{\rm s}=5$ ms, $I_{\rm rr}=0.3$ mW/mm$^2$), and the irradiance to $0.8 $ mW/mm$^2$ ($w_{\rm s}=5$ ms, $f=40$ Hz), respectively. In contrast, using the same analytical method, we find that Gaussian pulsed stimulation requires elevating the respective parameters (pulse width, frequency, irradiance) to $30$ ms, $250 $ Hz, and $1.9 $ mW/mm$^2$ for the effective suppression of seizure activity. Therefore, square-wave pulses require a smaller parameter threshold to achieve the effect of inhibiting epileptic seizures. From a physiological perspective, square-wave pulsed optogenetic stimulation is thus more suitable as a potential candidate for clinical trials.

Key words: optogenetic stimulation, square-wave pulse, Gaussian pulse, bifurcation analysis

中图分类号: (Ordinary differential equations (ODE), partial differential equations (PDE), integrodifferential models)

87.10.Ed

87.19.lj (Neuronal network dynamics) 87.19.ll (Models of single neurons and networks) 87.19.xm (Epilepsy)

Zhi-Hui Wang(王智慧), Jia-Hui Yang(杨佳慧), and Li-Xia Duan(段利霞). Targeted optogenetic stimulation of the thalamic reticular nucleus: A novel strategy for modulating epileptiform discharges[J]. 中国物理B, 2026, 35(6): 68701-068701.

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