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Optogenetic inhibition of the locus coeruleus blocks vagus nerve stimulation-induced enhancement of extinction of conditioned fear in rats.

作者信息

Calderon-Williams Debora R, de Souza Rimenez Rodrigues, Tseng Ching T, Abdi Hervé, Sandoval-Flores Alfredo, Ploski Jonathan E, Thorn Catherine A, McIntyre Christa K

机构信息

Department of Neuroscience, University of Texas at Dallas, Richardson, Texas 75080, USA.

Texas Biomedical Device Center, Richardson, Texas 75080, USA.

出版信息

Learn Mem. 2024 Dec 16;31(12). doi: 10.1101/lm.053958.124. Print 2024 Dec.


DOI:10.1101/lm.053958.124
PMID:39681462
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11662141/
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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aebc/11662141/8bc0dd526bc3/LM053958Cal_F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aebc/11662141/a1d7af04fca8/LM053958Cal_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aebc/11662141/5d6301a79619/LM053958Cal_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aebc/11662141/6165fed10bcc/LM053958Cal_F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aebc/11662141/8bc0dd526bc3/LM053958Cal_F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aebc/11662141/a1d7af04fca8/LM053958Cal_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aebc/11662141/5d6301a79619/LM053958Cal_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aebc/11662141/6165fed10bcc/LM053958Cal_F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aebc/11662141/8bc0dd526bc3/LM053958Cal_F4.jpg

相似文献

[1]
Optogenetic inhibition of the locus coeruleus blocks vagus nerve stimulation-induced enhancement of extinction of conditioned fear in rats.

Learn Mem. 2024-12-16

[2]
Rapid remission of conditioned fear expression with extinction training paired with vagus nerve stimulation.

Biol Psychiatry. 2012-12-13

[3]
Peripheral effects of vagus nerve stimulation on anxiety and extinction of conditioned fear in rats.

Learn Mem. 2019-6-17

[4]
Vagus nerve stimulation promotes extinction generalization across sensory modalities.

Neurobiol Learn Mem. 2021-5

[5]
Effects of vagus nerve stimulation on extinction of conditioned fear and post-traumatic stress disorder symptoms in rats.

Transl Psychiatry. 2017-8-22

[6]
Timing of vagus nerve stimulation during fear extinction determines efficacy in a rat model of PTSD.

Sci Rep. 2022-10-3

[7]
Vagus nerve stimulation reverses the extinction impairments in a model of PTSD with prolonged and repeated trauma.

Stress. 2019-4-23

[8]
Vagus nerve stimulation enhances fear extinction as an inverted-U function of stimulation intensity.

Exp Neurol. 2021-7

[9]
Vagus Nerve Stimulation Enhances Extinction of Conditioned Fear in Rats and Modulates Arc Protein, CaMKII, and GluN2B-Containing NMDA Receptors in the Basolateral Amygdala.

Neural Plast. 2016

[10]
Vagus nerve stimulation promotes generalization of conditioned fear extinction and reduces anxiety in rats.

Brain Stimul. 2018-9-21

引用本文的文献

[1]
A vagal route to memory: evidence from invasive and non-invasive electrical vagus nerve stimulation studies and areas for future clinical application.

Front Hum Neurosci. 2025-7-8

[2]
The Involvement of the Endocannabinoid, Glutamatergic, and GABAergic Systems in PTSD.

Int J Mol Sci. 2025-6-20

本文引用的文献

[1]
Frequency Specific Optogenetic Stimulation of the Locus Coeruleus Induces Task-Relevant Plasticity in the Motor Cortex.

J Neurosci. 2024-2-14

[2]
Vagus nerve stimulation parameters evoke differential neuronal responses in the locus coeruleus.

Physiol Rep. 2023-3

[3]
Acute Vagus Nerve Stimulation Facilitates Short Term Memory and Cognitive Flexibility in Rats.

Brain Sci. 2022-8-26

[4]
Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit.

Front Syst Neurosci. 2022-4-19

[5]
The ins and outs of the caudal nucleus of the solitary tract: An overview of cellular populations and anatomical connections.

J Neuroendocrinol. 2022-6

[6]
Daily Optogenetic Stimulation of the Left Infralimbic Cortex Reverses Extinction Impairments in Male Rats Exposed to Single Prolonged Stress.

Front Behav Neurosci. 2021-12-20

[7]
Local activation of α2 adrenergic receptors is required for vagus nerve stimulation induced motor cortical plasticity.

Sci Rep. 2021-11-4

[8]
Acute vagus nerve stimulation enhances reversal learning in rats.

Neurobiol Learn Mem. 2021-10

[9]
Vagus nerve stimulation enhances fear extinction as an inverted-U function of stimulation intensity.

Exp Neurol. 2021-7

[10]
Vagus nerve stimulation promotes extinction generalization across sensory modalities.

Neurobiol Learn Mem. 2021-5

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