Hulsey D, Shedd M, Mong J, Rennaker RL, Hays SA, Kilgard MP (2017) Vagus nerve stimulation dependent enhancement of motor cortex plasticity requires noradrenergic innervation. Neuroscience 2017 Abstracts 317.06 / HH5. Society for Neuroscience, Washington, DC.
Summary: Pairing forelimb movements with vagus nerve stimulation (VNS) drives robust plasticity within primary motor cortex (M1). VNS activates cholinergic circuits, which are required for VNS-depended enhancement of plasticity. However, there may be multiple neuromodulatory mechanisms required for VNS-dependent enhancement of plasticity. Norepinephrine regulates plasticity, and the noradrenergic locus coeruleus is driven vigorously by VNS. However, the role of norepinephrine in VNS-dependent enhancement of plasticity is unknown. We hypothesize that noradrenergic innervation of M1 and/or basal forebrain is necessary for M1 plasticity associated with VNS pairing. To test this, we trained rats on a skilled lever press task emphasizing use of the proximal forelimb. After demonstrating proﬁciency on the task, rats received M1 injections of vehicle or DBH-Saporin to selectively deplete norepinephrine in motor cortex, and underwent implantation of a stimulating cuﬀ electrode on the vagus nerve. Sham and NE- lesioned rats resumed training one week after surgery. After returning to pre-surgical performance, both groups received 10 sessions of training with VNS paired on successful trials. Intracortical microstimulation was performed to derive M1 maps within 24 hours of the ﬁnal training session. Initial data suggests that sham lesioned animals who receive VNS pairing with successful trials show a robust expansion of proximal forelimb movements represented in M1. Noradrenergic lesion of M1 blocks this VNS- dependent expansion of proximal forelimb representation, indicating that cortical norepinephrine innervation is necessary for VNS driven plasticity. Ongoing experiments will determine whether noradrenergic input to the central cholinergic systems is required for VNS-dependent enhancement of plasticity.
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