High intensity VNS disrupts VNS-mediated plasticity in motor cortex

• Published in: Brain research Vol. 1756; p. 147332
• Main Authors: Morrison, Robert A., Danaphongse, Tanya T., Abe, Stephanie T., Stevens, Madison E., Ezhil, Vikram, Seyedahmadi, Armin, Adcock, Katherine S., Rennaker, Robert L., Kilgard, Michael P., Hays, Seth A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2021
• Subjects: Animals; Cortical reorganization; Female; Intracortical microstimulation; Mastication - physiology; Motor cortex; Motor Cortex - physiology; Movement - physiology; Neurology; Neuronal Plasticity - physiology; Rats; Rats, Sprague-Dawley; Recovery of Function - physiology; Synaptic plasticity; Vagus nerve stimulation; Vagus Nerve Stimulation - methods; Vagus nerve stimulation; Intracortical microstimulation; Motor cortex; Cortical reorganization; Synaptic plasticity
• ISSN: 0006-8993; 1872-6240; 1872-6240
• DOI: 10.1016/j.brainres.2021.147332

•Moderate intensity VNS paired with training enhances synaptic plasticity.•High intensity VNS fails to enhance synaptic plasticity.•Interleaving moderate and high intensity VNS fails to enhance synaptic plasticity.•High intensity VNS disrupts mechanisms required for VNS-mediated plasticity.•High intensity stimulation blocks VNS-mediated plasticity for least 8 s. Vagus nerve stimulation (VNS) paired with motor rehabilitation enhances recovery of function after neurological injury in rats and humans. This effect is ascribed to VNS-dependent facilitation of plasticity in motor networks. Previous studies document an inverted-U relationship between VNS intensity and cortical plasticity, such that moderate intensities increase plasticity, while low or high intensity VNS does not. We tested the interaction of moderate and high intensity VNS trains to probe the mechanisms that may underlie VNS-dependent plasticity. Rats performed a behavioral task where VNS was paired with jaw movement during chewing. For five days, subjects received 100 pairings of moderate intensity VNS (Standard VNS), 100 pairings alternating between moderate and high intensity VNS (Interleaved VNS), or 50 pairings of moderate intensity VNS (Short VNS) approximately every 8 s. After the final behavioral session, intracortical microstimulation (ICMS) was used to evaluate movement representations in motor cortex. 100 pairings of moderate intensity VNS enhanced motor cortex plasticity. Replacing half of moderate intensity stimulation with high intensity VNS blocked this enhancement of plasticity. Removing high intensity stimulation, leaving only 50 pairings of moderate intensity VNS, reinstated plasticity. These results demonstrate that there is a period for at least 8 s after high intensity stimulation in which moderate intensity VNS is not able to engage mechanisms required for synaptic reorganization. More importantly, this study demonstrates that changes in stimulation parameters are a critical determinant of the magnitude of plasticity and likely the efficacy of VNS-enhanced recovery.