Background: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is considered to be the most relevant therapeutic option for patients with severe dystonias, which are thought to arise from a disturbance in striatal control of the GPi, possibly resulting in thalamic disinhibition. The mechanisms of GPi-DBS are far from understood. Hypotheses range from an overall silencing of target nuclei (due to e.g. depolarisation block), via differential alterations in thalamic firing, to disruption of oscillatory activity in the beta-range. Although a disturbance of striatal function is thought to play a key role in dystonia, the effects of DBS on cortico-striatal function are unknown. Objective: We hypothesised that DBS, via axonal backfiring, or indirectly via thalamic and cortical coupling, alters striatal network function. We aimed to test this hypothesis in the dtsz-hamster, an animal model of inherited generalised, paroxysmal dystonia. Methods: Hamsters (dtsz-dystonic and non-dystonic controls) were bilaterally implanted with stimulation electrodes targeting the entopeduncular nucleus (EPN, equivalent of human GPi). DBS (130 Hz), and sham DBS, were performed in unanaesthetised animals for 3 hours. Synaptic cortico-striatal field potential responses, as well as miniature excitatory postsynaptic currents (mEPSC) and firing properties of medium spiny striatal neurons were subsequently recorded in brain slice preparations obtained from these animals immediately after EPN-DBS, to gauge synaptic responsiveness of cortico-striatal projections, their inhibitory control, and striatal neuronal excitability. Results: DBS increased cortico-striatal responses in slices from control, but not dystonic animals. Inhibitory control of these responses, in turn, was differentially affected: DBS increased inhibitory control in dystonic, and decreased it in healthy tissue. A modulation of presynaptic mechanisms is likely involved, as mEPSC were reduced strongly in dystonic, and less prominently in healthy tissues, while cellular properties of medium-spiny neurons remained unchanged. Conclusion: DBS leads to dampening of cortico-striatal communication with restored inhibitory tone.

中文翻译：

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苍白的深脑刺激改变肌张力仓鼠的皮质纹状体突触通讯

背景：苍白苍白球（GPi）的深部脑刺激（DBS）被认为是重度肌张力障碍患者的最相关治疗选择，重度肌张力障碍被认为是由于GPi的纹状体控制障碍引起的，可能导致丘脑禁忌。GPi-DBS的机制远未了解。假设的范围从目标核的整体沉默（由于例如去极化阻滞），丘脑放电的差异改变到β范围内振荡活动的破坏。尽管认为纹状体功能障碍在肌张力障碍中起关键作用，但尚不清楚DBS对皮质-纹状体功能的影响。目的：我们假设DBS通过轴突背向射击或间接通过丘脑和皮层耦合改变纹状体网络功能。我们的目的是在dtsz-仓鼠（一种遗传的泛发性阵发性肌张力障碍的动物模型）中检验该假设。方法：向仓鼠（dtsz-肌张力障碍和非肌张力障碍对照）两侧植入靶向上皮单核（EPN，相当于人GPi）的刺激电极。在未麻醉的动物中进行DBS（130 Hz）和假DBS 3小时。随后在EPN-DBS后立即从这些动物获得的脑切片制剂中记录突触的皮质-纹状体场电位反应以及小型兴奋性突触后电流（mEPSC）和中突棘纹状神经元的放电特性，以评估皮质激素的突触反应性。纹状体投射，其抑制控制和纹状体神经元兴奋性。结果：DBS增加了对照切片的皮质-纹状体反应，但张力障碍动物却没有。这些反应的抑制控制又受到不同的影响：DBS增加了肌张力障碍的抑制控制，而降低了健康组织的抑制控制。可能牵涉到突触前机制的调节，因为肌张力障碍中的mEPSC明显降低，而健康组织中的mEPSC明显降低，而中棘神经元的细胞特性保持不变。结论：DBS可抑制皮质-纹状体沟通，抑制音调得以恢复。在健康组织中不那么明显，而中棘神经元的细胞特性保持不变。结论：DBS可抑制皮质-纹状体沟通，抑制音调得以恢复。在健康组织中不那么明显，而中棘神经元的细胞特性保持不变。结论：DBS可抑制皮质-纹状体沟通，抑制音调得以恢复。