ArticleLearning & memory (Cold Spring Harbor, N.Y.)2024
Optogenetic inhibition of the locus coeruleus blocks vagus nerve stimulation-induced enhancement of extinction of conditioned fear in rats.
Article in Learning & memory (Cold Spring Harbor, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Locus coeruleus-amygdala circuit disrupts prefrontal control to impair fear extinction.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Involvement of the Endocannabinoid, Glutamatergic, and GABAergic Systems in PTSD.International journal of molecular sciences · 2025Review
- A vagal route to memory: evidence from invasive and non-invasive electrical vagus nerve stimulation studies and areas for future clinical application.Frontiers in human neuroscience · 2025Review
- Neuromodulator timing regulates adult cortical plasticity via the synaptic eligibility trace.Brain stimulationArticle
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8 authors.
Funding
Abstract
Vagus nerve stimulation (VNS) is a therapeutic intervention previously shown to enhance fear extinction in rats. VNS is approved for use in humans for the treatment of epilepsy, depression, and stroke, and it is currently under investigation as an adjuvant to exposure therapy in the treatment of PTSD. However, the mechanisms by which VNS enhances extinction of conditioned fear remain unresolved. VNS increases norepinephrine levels in extinction-related pathways, but recent studies indicate that norepinephrine release from the locus coeruleus interferes with extinction learning. The purpose of this study is to elucidate the role of the locus coeruleus (LC) in VNS-enhanced fear extinction. Adult male and female tyrosine hydroxylase (Th)-Cre rats were implanted with a stimulating cuff electrode around the left cervical vagus nerve, and a Cre-dependent viral vector expressing the inhibitory opsin ArchT3.0 was infused bilaterally into the LC. Rats then underwent auditory fear conditioning followed by extinction training. During extinction training, rats were divided into four treatment groups: Sham stimulation, Sham with LC inhibition, VNS, and VNS with LC inhibition. Consistent with previous findings, VNS treatment during extinction training significantly reduced freezing 24 h and 2 weeks later. This effect was blocked by optogenetic LC inhibition, suggesting that VNS enhances extinction by engaging the LC.
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