Symptoms of neurological diseases emerge through the dysfunction of neural circuits whose diffuse and intertwined architectures pose serious challenges for delivering therapies. Deep brain stimulation (DBS) improves Parkinson’s disease symptoms acutely but does not differentiate between neuronal circuits, and its effects decay rapidly if stimulation is discontinued. Recent findings suggest that optogenetic manipulation of distinct neuronal subpopulations in the external globus pallidus (GPe) provides long-lasting therapeutic effects in dopamine-depleted (DD) mice. We used synaptic differences to excite parvalbumin-expressing GPe neurons and inhibit lim-homeobox-6–expressing GPe neurons simultaneously using brief bursts of electrical stimulation. In DD mice, circuit-inspired DBS provided long-lasting therapeutic benefits that far exceeded those induced by conventional DBS, extending several hours after stimulation. These results establish the feasibility of transforming knowledge of circuit architecture into translatable therapeutic approaches.

中文翻译：

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人群特异性神经调节可延长深部脑刺激的治疗效果


神经系统疾病的症状是通过神经回路功能障碍而出现的，神经回路分散且交织的结构给治疗带来了严峻的挑战。深部脑刺激（DBS）可以显着改善帕金森病的症状，但不能区分神经元回路，如果停止刺激，其效果会迅速减弱。最近的研究结果表明，对外苍白球（GPe）中不同神经元亚群的光遗传学操作可以为多巴胺耗尽（DD）小鼠提供持久的治疗效果。我们利用突触差异来激发表达小白蛋白的 GPe 神经元，并使用短暂的电刺激同时抑制表达 lim-homeobox-6 的 GPe 神经元。在 DD 小鼠中，电路激发的 DBS 提供了远远超过传统 DBS 诱导的持久治疗效果，刺激后持续数小时。这些结果确立了将电路架构知识转化为可转化治疗方法的可行性。