脑深部刺激诱导的两种消除帕金森病爆发的方式:突触电流和分叉机制。

IF 3.1 3区 工程技术 Q2 NEUROSCIENCES
Cognitive Neurodynamics Pub Date : 2025-12-01 Epub Date: 2025-05-19 DOI:10.1007/s11571-025-10267-5
Hui Zhou, Xianjun Wang, Huaguang Gu, Yanbing Jia
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引用次数: 0

摘要

脑深部电刺激(DBS)是治疗帕金森病(PD)的有效方法,但其作用机制尚不清楚。本文研究了基底节区-丘脑模型的动力学机制和突触机制。首先,确定突触门控变量/电流的缓慢和大振荡是PD不规则和非同步爆发的原因,表明中断这些缓慢调制可能是治疗PD的可行措施。其次,高频强DBS作用于丘脑底核(STN),可引起STN和外白球(GPe)的快速同步尖峰,然后中断慢门控变量,从而消除不规则爆发。同时,从STN和GPe到内部苍白球(GPi)的兴奋性突触和抑制性突触的门控变量变快。最后,这两个相反的突触之间的竞争可以诱导两种方式消除GPi的破裂并恢复正常状态,出现在绝大多数由多个突触电导组成的参数空间中。一种是GPi的同步沉默,另一种是同步规律的快速尖峰,分别发生在抑制性突触和兴奋性突触的大电导下。两者都通过中断投射到丘脑的突触的缓慢门控变量,导致丘脑的定期尖峰。此外,当两个电导相互接近时,GPi的突触电流在零附近缓慢振荡,导致GPi和丘脑在狭窄的参数空间内不规则地放电。此外,利用极限环的鞍节点分岔和突触电流的振荡模式,解释了DBS前PD中观察到的爆发和DBS期间GPi的三种电活动。讨论了与以往研究报道的抑制后反弹爆发的区别。研究结果揭示了DBS通过消除宽参数区爆裂来治疗PD的机理。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Deep brain stimulation-induced two manners to eliminate bursting for Parkinson's diseases: synaptic current and bifurcation mechanisms.

Although deep brain stimulation (DBS) is effective in treating Parkinson's disease (PD) related to bursting, the underlying mechanisms remain unclear. In the present paper, the dynamical and synaptic mechanisms are studied in a basal ganglia-thalamus model. Firstly, slow and large oscillations of synaptic gating variables/currents are identified as the cause of the irregular and non-synchronous bursting for PD, indicating that interruption of these slow modulations may be a feasible measure to treat PD. Secondly, strong DBS with high frequency applied to subthalamic nucleus (STN) can induce fast synchronous spiking in both STN and external globus pallidus (GPe), then interrupt the slow gating variables, thereby eliminating the irregular bursting. Meanwhile, the gating variables of the excitatory and inhibitory synapses respectively from STN and GPe to the internal globus pallidus (GPi) become fast. Finally, competition between these two opposite synapses can induce two manners to eliminate the bursting of GPi and restore the normal state, appearing in vast majority of parameter space composed of multiple synaptic conductances. One is the synchronous silence of GPi, and the other the synchronous regular fast spiking, which occurs for large conductance of the inhibitory and excitatory synapse, respectively. Both result in regular spiking of thalamus, via interrupting slow gating variables of synapse projected to thalamus. In addition, as the two conductances approach each other, the synaptic current to GPi oscillates around zero slowly, resulting in irregular firings of GPi and thalamus for PD in a narrow parameter space. Furthermore, the bursting observed in PD before DBS and three types of electrical activities of GPi during DBS are explained, using a saddle-node bifurcation of limit cycles and oscillation patterns of synaptic current. The distinction from the post inhibitory rebound bursting reported in previous studies is discussed. The results present the mechanisms for DBS to treat PD via eliminating bursting in wide parameter region.

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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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