Vagus nerve stimulation intensity influences motor cortex plasticity

Morrison, Robert A.; Hulsey, Daniel R.; Adcock, Katherine S.; Rennaker, Robert L.; Kilgard, Michael P.; Hays, Seth A.

doi:10.1016/j.brs.2018.10.017

Cited by 73 publications

(61 citation statements)

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“…Previous studies have demonstrated that VNS during rehabilitative training improves recovery of motor function in several models of brain injury (Khodaparast et al, 2016, 2014; Hays et al, 2014a,b, 2016; Meyers et al, 2018; Morrison et al, 2019). The therapeutic effects of pairing VNS with motor rehabilitation persist even after the cessation of stimulation, suggesting that the VNS-induced plasticity and learning are long-term (Khodaparast et al, 2014; Hays et al, 2014a).…”

Section: Introductionmentioning

confidence: 99%

Short-term Effects of Vagus Nerve Stimulation on Learning and Evoked Activity in Auditory Cortex

Lai

David

2019

Preprint

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2Chronic vagus nerve stimulation (VNS) can facilitate learning of sensory and motor behaviors. 3 VNS is believed to trigger release of neuromodulators, including norepinephrine and acetylcholine, 4 which can mediate cortical plasticity associated with learning. Most previous work has studied 5 effects of VNS over many days, and less is known about how acute VNS influences neural coding 6 and behavior over the shorter term. To explore this question, we measured effects of VNS on 7 learning of an auditory discrimination over 1-2 days. Ferrets implanted with cuff electrodes on 8 the vagus nerve were trained by classical conditioning on a tone frequency-reward association. 9 One tone was associated with reward while another tone, was not. The frequencies and reward 10 associations of the tones were changed every two days, requiring learning of a new relationship. 11 When the tones (both rewarded and non-rewarded) were paired with VNS, rates of learning 12 increased on the first day following a change in reward association. To examine VNS effects 13 on auditory coding, we recorded single-and multi-unit neural activity in primary auditory cortex 14 (A1) of passively listening animals following brief periods of VNS (20 trials/session) paired with 15 tones. Because afferent VNS induces changes in pupil size associated with fluctuations in 16 neuromodulation, we also measured pupil during recordings. After pairing VNS with a neuron's 17 1 Jesyin Lai Short-term VNSbest-frequency (BF) tone, responses in a subpopulation of neurons were reduced. Pairing with 18 an off-BF tone or performing VNS during the inter-trial interval had no effect on responses. 19 We separated the change in A1 activity into two components, one that could be predicted by 20 fluctuations in pupil and one that persisted after VNS and was not accounted for by pupil. The 21 BF-specific reduction in neural responses remained, even after regressing out changes that 22 could be explained by pupil. In addition, the size of VNS-mediated changes in pupil predicted the 23 magnitude of persistent changes in the neural response. This interaction suggests that changes 24 in neuromodulation associated with arousal gate the long-term effects of VNS on neural activity. 25 Taken together, these results support a role for VNS in auditory learning and help establish VNS 26 as a tool to facilitate neural plasticity. 27 28

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Section: Introductionmentioning

confidence: 99%

Short-term Effects of Vagus Nerve Stimulation on Learning and Evoked Activity in Auditory Cortex

Lai

David

2019

Preprint

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“…Rats were trained on a skilled motor task, as in previous studies [15][16][17]23]. The task was an automated lever pressing task, in which the animal was required to learn to reach outside of a cage and press a lever twice in rapid succession.…”

Section: Motor Behavioral Testingmentioning

confidence: 99%

“…The task was an automated lever pressing task, in which the animal was required to learn to reach outside of a cage and press a lever twice in rapid succession. The behavior apparatus consisted of an acrylic cage, with a slot in the front right for access to a lever that was positioned 1 (inside) to 2 cm (outside) away from inside the edge of the chamber [15][16][17]23] ( Fig. 2a).…”

Section: Motor Behavioral Testingmentioning

confidence: 99%

Deficits in skilled motor and auditory learning in a rat model of Rett syndrome

Adcock

Blount

Morrison

et al. 2020

J Neurodevelop Disord

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Background Rett syndrome is an X-linked neurodevelopmental disorder caused by a mutation in the gene MECP2. Individuals with Rett syndrome display developmental regression at an early age, and develop a range of motor, auditory, cognitive, and social impairments. Several studies have successfully modeled some aspects of dysfunction and Rett syndrome-like phenotypes in transgenic mouse and rat models bearing mutations in the MECP2 gene. Here, we sought to extend these findings and characterize skilled learning, a more complex behavior known to be altered in Rett syndrome. Methods We evaluated the acquisition and performance of auditory and motor function on two complex tasks in heterozygous female Mecp2 rats. Animals were trained to perform a speech discrimination task or a skilled forelimb reaching task. Results Our results reveal that Mecp2 rats display slower acquisition and reduced performance on an auditory discrimination task than wild-type (WT) littermates. Similarly, Mecp2 rats exhibit impaired learning rates and worse performance on a skilled forelimb motor task compared to WT. Conclusions Together, these findings illustrate novel deficits in skilled learning consistent with clinical manifestation of Rett syndrome and provide a framework for development of therapeutic strategies to improve these complex behaviors.

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“…Rats were trained on a skilled motor task, as in previous studies (Hays et al, 2013;Hulsey et al, 2016Hulsey et al, , 2019Morrison et al, 2019). The task was an automated lever pressing task, in which the animal was required to learn to reach outside of a cage and press a lever twice in rapid succession.…”

Section: Motor Behavioral Testingmentioning

confidence: 99%

Deficits in Skilled Motor and Auditory Learning in a Rat Model of Rett Syndrome

Adcock¹,

Blount

Morrison³

et al. 2020

Preprint

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Background Rett Syndrome is an X-linked neurodevelopmental disorder caused by a mutation in the gene MECP2 . Individuals with Rett Syndrome display developmental regression at an early age, and develop a range of motor, auditory, cognitive and social impairments. Several studies have successfully modeled some aspects of dysfunction and Rett Syndrome-like phenotypes in transgenic mouse and rat models bearing mutations in the MECP2 gene. Here, we sought to extend these findings and characterize skilled learning, a more complex behavior known to be altered in Rett syndrome. Methods We evaluated the acquisition and performance of auditory and motor function on two complex tasks in heterozygous female Mecp2 rats. Animals were trained to perform a speech discrimination task or a skilled forelimb reaching task. Results Our results reveal that Mecp2 rats display slower acquisition and reduced performance on an auditory discrimination task than wild-type (WT) littermates. Similarly, Mecp2 rats exhibit impaired learning rates and worse performance on a skilled forelimb motor task compared to WT. Conclusions Together, these findings illustrate novel deficits in skilled learning consistent with clinical manifestation of Rett syndrome and provide a framework for development of therapeutic strategies to improve these complex behaviors.

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Vagus nerve stimulation intensity influences motor cortex plasticity

Cited by 73 publications

References 50 publications

Short-term Effects of Vagus Nerve Stimulation on Learning and Evoked Activity in Auditory Cortex

Short-term Effects of Vagus Nerve Stimulation on Learning and Evoked Activity in Auditory Cortex

Deficits in skilled motor and auditory learning in a rat model of Rett syndrome

Deficits in Skilled Motor and Auditory Learning in a Rat Model of Rett Syndrome

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