Numerous preclinical studies demonstrate that vagus nerve stimulation (VNS) paired with motor rehabilitation improves functional recovery after neural injuries such as stroke, traumatic brain injury, and spinal cord injury, in part by driving neural plasticity within the motor cortex. To date, these studies have been performed almost exclusively in female rats, however, the risk for neural injuries of all types is significantly higher among males than females. We therefore sought to determine whether VNS was equally effective at driving motor cortical plasticity in both sexes. Male and female rats were trained on a skilled lever press task prior to VNS electrode implantation. After recovery, rats received ten training sessions in which VNS, or sham stimulation, was paired with correct motor performance. At the completion of these treatment sessions, somatotopic mapping of motor cortex was performed. We found that performance on the lever task was similar between male and female rats, though on average, males performed more trials per training session, consistent with their larger size and higher caloric need. Training-paired VNS effectively induced cortical motor map reorganization in both male and female rats. Notably, we also found that VNS reduced lever-press associated caloric intake during treatment in both sexes. These VNS-driven effects were robust to behavioral and biological differences between male and female subjects. Taken together, our results suggest that, in both male and female rats, VNS simultaneously engages both pro-plasticity neuromodulation within the neocortex and satiety or reward-related networks that reduce task-associated caloric intake.

大量临床前研究表明，迷走神经刺激 (VNS) 与运动康复相结合可改善中风、创伤性脑损伤和脊髓损伤等神经损伤后的功能恢复，部分原因是通过驱动运动皮层内的神经可塑性。迄今为止，这些研究几乎只在雌性大鼠中进行，然而，所有类型神经损伤的风险在雄性大鼠中明显高于雌性。因此，我们试图确定 VNS 在驱动两性运动皮质可塑性方面是否同样有效。在 VNS 电极植入之前，对雄性和雌性大鼠进行了熟练的杠杆按压任务训练。恢复后，大鼠接受了 10 次训练，其中 VNS 或假刺激与正确的运动表现配对。在这些治疗期结束时，进行运动皮层的体位映射。我们发现雄性和雌性大鼠在杠杆任务上的表现相似，尽管平均而言，雄性在每次训练中进行了更多的试验，这与其更大的体型和更高的热量需求一致。训练配对 VNS 有效诱导雄性和雌性大鼠的皮质运动图重组。值得注意的是，我们还发现 VNS 在治疗期间减少了与杠杆按压相关的热量摄入。这些 VNS 驱动的效应对男性和女性受试者之间的行为和生物学差异具有强大的影响。总之，我们的结果表明，在雄性和雌性大鼠中，