Background: Vagus nerve stimulation (VNS) paired with motor rehabilitation is an emerging therapeutic strategy to enhance functional recovery after neural injuries such as stroke. Training-paired VNS drives significant neuroplasticity within the motor cortex (M1), which is thought to underlie the therapeutic effects of VNS. Though the mechanisms are not fully understood, VNS-induced cortical plasticity is known to depend on intact signaling from multiple neuromodulatory nuclei that innervate M1. Cortical dopamine (DA) plays a key role in mediating M1 synaptic plasticity and is critical for motor skill acquisition, but whether cortical DA contributes to VNS efficacy has not been tested. Objective: To determine the impact of cortical DA depletion on VNS-induced cortical plasticity. Methods: Rats were trained on a skilled reaching lever press task prior to implantation of VNS electrodes and 6-hydroxydopamine (6-OHDA) mediated DA depletion in M1. Rats then underwent training-paired VNS treatment, followed by cortical motor mapping and lesion validation. Results: In both intact and DA-depleted rats, VNS significantly increased the motor map representation of task-relevant proximal forelimb musculature and reduced task-irrelevant distal forelimb representations. VNS also significantly increased tyrosine hydroxylase (TH+) fiber density in intact M1, but this effect was not observed in lesioned hemispheres. Conclusion: Our results reveal that though VNS likely upregulates catecholaminergic signaling in intact motor cortices, DA itself is not required for VNS-induced plasticity to occur. As DA is known to critically support M1 plasticity during skill acquisition, our findings suggest that VNS may engage a unique set of neuromodulatory signaling pathways to promote neocortical plasticity.

中文翻译：

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迷走神经刺激引起的运动图可塑性不需要皮质多巴胺。

背景：迷走神经刺激 (VNS) 与运动康复相结合是一种新兴的治疗策略，可增强中风等神经损伤后的功能恢复。训练配对 VNS 驱动运动皮层 (M1) 内的显着神经可塑性，这被认为是 VNS 治疗效果的基础。虽然机制尚不完全清楚，但已知 VNS 诱导的皮质可塑性取决于来自支配 M1 的多个神经调节核的完整信号。皮质多巴胺 (DA) 在介导 M1 突触可塑性中起关键作用，对运动技能的习得至关重要，但皮质 DA 是否有助于 VNS 功效尚未得到测试。目的：确定皮质 DA 耗竭对 VNS 诱导的皮质可塑性的影响。方法：在植入 VNS 电极和 6-羟基多巴胺 (6-OHDA) 介导 M1 中的 DA 消耗之前，大鼠接受了熟练的杠杆按压任务。然后大鼠接受训练配对 VNS 治疗，然后进行皮层运动映射和病变验证。结果：在完整和 DA 耗尽的大鼠中，VNS 显着增加了与任务相关的近端前肢肌肉组织的运动图表示，并减少了与任务无关的远端前肢表示。VNS 还显着增加了完整 M1 中的酪氨酸羟化酶 (TH+) 纤维密度，但在受损半球中未观察到这种效果。结论：我们的结果表明，虽然 VNS 可能上调完整运动皮质中的儿茶酚胺能信号传导，但 DA 本身并不是 VNS 诱导的可塑性发生所必需的。