Vagus Nerve Stimulation Enhances Extinction of Conditioned Fear in Rats and Modulates Arc Protein, CaMKII, and GluN2B-Containing NMDA Receptors in the Basolateral Amygdala

Vagus nerve stimulation (VNS) enhances the consolidation of extinction of conditioned fear. High frequency stimulation of the infralimbic cortex (IL) produces long-term potentiation in the basolateral amygdala (BLA) in rats given VNS-paired extinction training, whereas the same stimulation produces long-term depression in sham-treated rats. The present study investigated the state of synaptic plasticity-associated proteins in the BLA that could be responsible for this shift. Male Sprague-Dawley rats were separated into 4 groups: auditory fear conditioning only (fear-conditioned); fear conditioning + 20 extinction trials (extended-extinction); fear conditioning + 4 extinction trials paired with sham stimulation (sham-extinction); fear conditioning + 4 extinction trials paired with VNS (VNS-extinction). Freezing was significantly reduced in extended-extinction and VNS-extinction rats. Western blots were used to quantify expression and phosphorylation state of synaptic plasticity-associated proteins such as Arc, CaMKII, ERK, PKA, and AMPA and NMDA receptors. Results show significant increases in GluN2B expression and phosphorylated CaMKII in BLA samples from VNS- and extended-extinction rats. Arc expression was significantly reduced in VNS-extinction rats compared to all groups. Administration of the GluN2B antagonist ifenprodil immediately after fear extinction training blocked consolidation of extinction learning. Results indicate a role for BLA CaMKII-induced GluN2B expression and reduced Arc protein in VNS-enhanced extinction.

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Long Term Effects of Low Frequency (10 Hz) Vagus Nerve Stimulation on EEG and Heart Rate Variability in Crohn's Disease: A Case Report

Brain Stimulation ◽

10.1016/j.brs.2014.08.001 ◽

2014 ◽

Vol 7 (6) ◽

pp. 914-916 ◽

Cited By ~ 26

Author(s):

Didier Clarençon ◽

Sonia Pellissier ◽

Valérie Sinniger ◽

Astrid Kibleur ◽

Dominique Hoffman ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Crohn’S Disease ◽

Case Report ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Low Frequency ◽

Long Term Effects

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Vagus nerve stimulation for drug-resistant epilepsy

Practical Neurology ◽

10.1136/practneurol-2019-002210 ◽

2019 ◽

Vol 20 (3) ◽

pp. 189-198 ◽

Cited By ~ 1

Author(s):

Laura Pérez-Carbonell ◽

Howard Faulkner ◽

Sean Higgins ◽

Michalis Koutroumanidis ◽

Guy Leschziner

Keyword(s):

Vagus Nerve ◽

Seizure Frequency ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Therapeutic Option ◽

Drug Resistant ◽

Drug Resistant Epilepsy ◽

Randomised Controlled

Vagus nerve stimulation (VNS) is a neuromodulatory therapeutic option for drug-resistant epilepsy. In randomised controlled trials, VNS implantation has resulted in over 50% reduction in seizure frequency in 26%–40% of patients within 1 year. Long-term uncontrolled studies suggest better responses to VNS over time; however, the assessment of other potential predictive factors has led to contradictory results. Although initially designed for managing focal seizures, its use has been extended to other forms of drug-resistant epilepsy. In this review, we discuss the evidence supporting the use of VNS, its impact on seizure frequency and quality of life, and common adverse effects of this therapy. We also include practical guidance for the approach to and the management of patients with VNS in situ.

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Letter to the editor regarding the article “Assessment for vagus nerve stimulation in patients with difficult-to-treat depression: A model from the newcastle regional affective disorders service (RADS)” vagus nerve stimulation (VNS) in patients with difficult-to-treat depression – long-term outcome is improved but who are the right candidates for VNS?

Journal of Affective Disorders ◽

10.1016/j.jad.2020.12.006 ◽

2021 ◽

Vol 281 ◽

pp. 90

Author(s):

Helge H.O. Müller ◽

Sebastian Moeller

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Affective Disorders ◽

Vagus Nerve Stimulation ◽

Term Outcome ◽

Long Term Outcome ◽

Letter To The Editor ◽

The Right

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Long term effect of vagus nerve stimulation in pediatric intractable epilepsy: an extended follow-up

Child s Nervous System ◽

10.1007/s00381-015-3004-z ◽

2016 ◽

Vol 32 (4) ◽

pp. 641-646 ◽

Cited By ~ 24

Author(s):

Ayse Serdaroglu ◽

Ebru Arhan ◽

Gökhan Kurt ◽

Atilla Erdem ◽

Tugba Hirfanoglu ◽

...

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Intractable Epilepsy ◽

Term Effect ◽

Long Term Effect

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Promoting long-term inhibition of human fear responses by non-invasive transcutaneous vagus nerve stimulation during extinction training

Scientific Reports ◽

10.1038/s41598-020-58412-w ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 4

Author(s):

Christoph Szeska ◽

Jan Richter ◽

Julia Wendt ◽

Mathias Weymar ◽

Alfons O. Hamm

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Extinction Training ◽

Non Invasive ◽

Transcutaneous Vagus Nerve Stimulation

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Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Stroke: One-Year Follow-up

Neurorehabilitation and Neural Repair ◽

10.1177/1545968320924361 ◽

2020 ◽

Vol 34 (7) ◽

pp. 609-615

Author(s):

Jesse Dawson ◽

Navzer D. Engineer ◽

Cecília N. Prudente ◽

David Pierce ◽

Gerard Francisco ◽

...

Keyword(s):

Ischemic Stroke ◽

Vagus Nerve ◽

Upper Limb ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Exercise Program ◽

Home Exercise ◽

Home Exercise Program

Background. Vagus nerve stimulation (VNS) paired with rehabilitation may improve upper-limb impairment and function after ischemic stroke. Objective. To report 1-year safety, feasibility, adherence, and outcome data from a home exercise program paired with VNS using long-term follow-up data from a randomized double-blind study of rehabilitation therapy paired with Active VNS (n = 8) or Control VNS (n = 9). Methods. All people were implanted with a VNS device and underwent 6 weeks in clinic therapy with Control or Active VNS followed by home exercises through day 90. Thereafter, participants and investigators were unblinded. The Control VNS group then received 6 weeks in-clinic Active VNS (Cross-VNS group). All participants then performed an individualized home exercise program with self-administered Active VNS. Data from this phase are reported here. Outcome measures were Fugl-Meyer Assessment—Upper Extremity (FMA-UE), Wolf Motor Function Test (Functional and Time), Box and Block Test, Nine-Hole Peg Test, Stroke Impact Scale, and Motor Activity Log. Results. There were no VNS treatment–related serious adverse events during the long-term therapy. Two participants discontinued prior to receiving the full crossover VNS. On average, participants performed 200 ± 63 home therapy sessions, representing device use on 57.4% of home exercise days available for each participant. Pooled analysis revealed that 1 year after randomization, the FMA-UE score increased by 9.2 points (95% CI = 4.7 to 13.7; P = .001; n = 15). Other functional measures were also improved at 1 year. Conclusions. VNS combined with rehabilitation is feasible, with good long-term adherence, and may improve arm function after ischemic stroke.

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