Local activation of α2 adrenergic receptors is required for vagus nerve stimulation induced motor cortical plasticity

Vagus nerve stimulation (VNS) paired with rehabilitation training is emerging as a potential treatment for improving recovery of motor function following stroke. In rats, VNS paired with skilled forelimb training results in significant reorganization of the somatotopic cortical motor map; however, the mechanisms underlying this form of VNS-dependent plasticity remain unclear. Recent studies have shown that VNS-driven cortical plasticity is dependent on noradrenergic innervation of the neocortex. In the central nervous system, noradrenergic alpha 2 receptors (alpha 2-ARs) are widely expressed in the motor cortex and have been critically implicated in synaptic communication and plasticity. In current study, we examined whether activation of cortical alpha 2-ARs is necessary for VNS-driven motor cortical reorganization to occur. Consistent with previous studies, we found that VNS paired with motor training enlarges the map representation of task-relevant musculature in the motor cortex. Infusion of alpha 2-AR antagonists into M1 blocked VNS-driven motor map reorganization from occurring. Our results suggest that local alpha 2-AR activation is required for VNS-induced cortical reorganization to occur, providing insight into the mechanisms that may underlie the neuroplastic effects of VNS therapy.

Automated summary

Vagus nerve stimulation paired with motor training enhances the map representation of task-relevant musculature in the motor cortex, with activation of cortical alpha 2 receptors being necessary for this motor cortical reorganization to occur.