Striatum is the potential target for treating absence epilepsy: a theoretical evidence

IF 3.1 3区 工程技术 Q2 NEUROSCIENCES
Bing Hu, Weiting Zhou, Xunfu Ma
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Abstract

The output of the basal ganglia to the corticothalamic system plays an important role in regulating absence seizures. Inspired by experiments, we systematically study the crucial roles of two newly identified direct inhibitory striatal-cortical projections that project from the striatal D1 nucleus (SD1) and striatal D2 nucleus (SD2) to the cerebral cortex, in controlling absence seizures. Through computational simulation, we observe that typical 2–4 Hz spike and wave discharges (SWDs) can be induced through the pathological mechanism of cortical circuits, and both enhancing the inhibitory coupling weight on the striatal-cortical projections and improving the discharge activation level of striatal populations can effectively control typical SWDs. Furthermore, typical SWDs can be suppressed by appropriately adjusting several input projections directly related to the striatum, through regulating the activation level of striatal populations. Interestingly, several indirect striatum-related basal ganglia projections also have significant effects on the inhibition of typical SWDs, through the direct inhibitory striatal-cortical projections. Both the unidirectional control mode and bidirectional control mode for typical SWDs exist in our modified model. Importantly, the enhancement of coupling strengths on inhibitory striatal-cortical projections is beneficial for suppressing SWDs and may play a decisive regulatory role in the formation of control modes. Therefore, our study suggests that striatum may be potential effective targets for the treatment of absence seizures, through two newly identified direct inhibitory striatal-cortical projections. Interestingly, we find that external stimuli simultaneously targeting the striatum and another basal ganglia nucleus have a better control effect on SWDs than targeting a single basal ganglia nucleus, and the obtained results provide testable hypotheses for future experiments.

Abstract Image

纹状体是治疗失神性癫痫的潜在靶点:理论证据
基底节向皮质-丘脑系统的输出在失神发作的调节中起着重要作用。受实验启发,我们系统地研究了两个新发现的纹状体-皮层直接抑制性投射,它们分别从纹状体 D1 核(SD1)和纹状体 D2 核(SD2)投射到大脑皮层,在控制失神发作中的关键作用。通过计算模拟,我们观察到典型的2-4赫兹尖波放电(SWDs)可通过皮层回路的病理机制诱发,而增强纹状体-皮层投射的抑制耦合权重和提高纹状体群的放电激活水平均可有效控制典型的SWDs。此外,通过调节纹状体群的激活水平,适当调整与纹状体直接相关的几个输入投射,也可以抑制典型的 SWD。有趣的是,通过纹状体-皮层的直接抑制性投射,几个与纹状体间接相关的基底节投射也对典型 SWDs 的抑制有显著效果。在我们改进的模型中,典型 SWD 的单向控制模式和双向控制模式都存在。重要的是,抑制性纹状体-皮层投射耦合强度的增强有利于抑制SWD,并可能在控制模式的形成过程中起到决定性的调节作用。因此,我们的研究表明,纹状体可能通过两个新发现的直接抑制性纹状体-皮层投射成为治疗失神发作的潜在有效靶点。有趣的是,我们发现同时针对纹状体和另一个基底节细胞核的外部刺激比针对单一基底节细胞核的外部刺激对失神发作有更好的控制效果。
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来源期刊
Cognitive Neurodynamics
Cognitive Neurodynamics 医学-神经科学
CiteScore
6.90
自引率
18.90%
发文量
140
审稿时长
12 months
期刊介绍: Cognitive Neurodynamics provides a unique forum of communication and cooperation for scientists and engineers working in the field of cognitive neurodynamics, intelligent science and applications, bridging the gap between theory and application, without any preference for pure theoretical, experimental or computational models. The emphasis is to publish original models of cognitive neurodynamics, novel computational theories and experimental results. In particular, intelligent science inspired by cognitive neuroscience and neurodynamics is also very welcome. The scope of Cognitive Neurodynamics covers cognitive neuroscience, neural computation based on dynamics, computer science, intelligent science as well as their interdisciplinary applications in the natural and engineering sciences. Papers that are appropriate for non-specialist readers are encouraged. 1. There is no page limit for manuscripts submitted to Cognitive Neurodynamics. Research papers should clearly represent an important advance of especially broad interest to researchers and technologists in neuroscience, biophysics, BCI, neural computer and intelligent robotics. 2. Cognitive Neurodynamics also welcomes brief communications: short papers reporting results that are of genuinely broad interest but that for one reason and another do not make a sufficiently complete story to justify a full article publication. Brief Communications should consist of approximately four manuscript pages. 3. Cognitive Neurodynamics publishes review articles in which a specific field is reviewed through an exhaustive literature survey. There are no restrictions on the number of pages. Review articles are usually invited, but submitted reviews will also be considered.
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