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恐惧消退过程中刺激迷走神经的时机决定了 PTSD 大鼠模型中的疗效。

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

机构信息

Texas Biomedical Device Center, The University of Texas at Dallas, Richardson, TX, 75080, USA.

School of Behavioral Brain Sciences, The University of Texas at Dallas, Bioengineering and Sciences Building, 14.506, 800 West Campbell Road, Richardson, TX, 75080, USA.

出版信息

Sci Rep. 2022 Oct 3;12(1):16526. doi: 10.1038/s41598-022-20301-9.


DOI:10.1038/s41598-022-20301-9
PMID:36192564
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9530175/
Abstract

Studies have indicated that vagus nerve stimulation (VNS) enhances extinction learning in rodent models. Here, we investigated if pairing VNS with the conditioned stimulus is required for the enhancing effects of VNS. Adult Sprague-Dawley rats were exposed to intense stress followed by fear conditioning training to produce resistant fear. Rats were then implanted with a cuff electrode around the left vagus. After recovery, rats underwent extinction training paired with VNS (0.5 s, 0.8 mA, 100 µs, and 30 Hz) or with Sham VNS (0 mA). VNS rats were randomized into the following subgroups: During VNS (delivered during presentations of the conditioned stimulus, CS), Between VNS (delivered between CS presentations), Continuous VNS (delivered during the entire extinction session), and Dispersed VNS (delivered at longer inter-stimulation intervals across the extinction session). Sham VNS rats failed to extinguish the conditioned fear response over 5 days of repeated exposure to the CS. Rats that received Between or Dispersed VNS showed modest improvement in conditioned fear at the retention test. During and Continuous VNS groups displayed the greatest reduction in conditioned fear. These findings indicate that delivering VNS paired precisely with CS presentations or continuously throughout extinction promotes the maximum enhancement in extinction learning.

摘要

研究表明,迷走神经刺激(VNS)可增强啮齿动物模型中的消退学习。在这里,我们研究了 VNS 与条件刺激配对是否是 VNS 增强效应所必需的。成年 Sprague-Dawley 大鼠接受强烈的应激,然后进行恐惧条件训练以产生抵抗性恐惧。然后,将大鼠的左迷走神经周围放置一个袖带电极。恢复后,大鼠进行消退训练,同时进行 VNS(0.5 s、0.8 mA、100 µs 和 30 Hz)或假 VNS(0 mA)。VNS 大鼠随机分为以下亚组:在 VNS 期间(在条件刺激 CS 呈现期间给予)、在 VNS 之间(在 CS 呈现之间给予)、连续 VNS(在整个消退过程中给予)和分散 VNS(在消退过程中以较长的刺激间隔给予)。假 VNS 大鼠在重复暴露于 CS 的 5 天内未能消除条件性恐惧反应。接受在 VNS 之间或分散 VNS 的大鼠在保留测试中表现出对条件性恐惧的适度改善。在 VNS 和连续 VNS 组中,条件性恐惧的减少最为明显。这些发现表明,与 CS 呈现精确配对或在整个消退过程中持续给予 VNS 可促进消退学习的最大增强。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f021/9530175/ab8326c6a808/41598_2022_20301_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f021/9530175/6039b353ccae/41598_2022_20301_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f021/9530175/623e8b19c324/41598_2022_20301_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f021/9530175/cf3e780009ff/41598_2022_20301_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f021/9530175/a73b17d5bc72/41598_2022_20301_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f021/9530175/ab8326c6a808/41598_2022_20301_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f021/9530175/6039b353ccae/41598_2022_20301_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f021/9530175/623e8b19c324/41598_2022_20301_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f021/9530175/cf3e780009ff/41598_2022_20301_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f021/9530175/a73b17d5bc72/41598_2022_20301_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f021/9530175/ab8326c6a808/41598_2022_20301_Fig5_HTML.jpg

相似文献

[1]
Timing of vagus nerve stimulation during fear extinction determines efficacy in a rat model of PTSD.

Sci Rep. 2022-10-3

[2]
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[3]
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[4]
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[5]
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[2]
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[3]
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[4]
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Front Syst Neurosci. 2024-12-24

[5]
REM disruption and REM vagal activity predict extinction recall in trauma-exposed individuals.

Psychol Med. 2024-12-9

[6]
Non-Invasive Vagal Nerve Stimulation Pre-Treatment Reduces Neurological Dysfunction After Closed Head Injury in Mice.

Neurotrauma Rep. 2024-2-29

[7]
Dorsal motor vagal neurons can elicit bradycardia and reduce anxiety-like behavior.

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[8]
REM disruption and REM Vagal Activity Predict Extinction Recall in Trauma-Exposed Individuals.

bioRxiv. 2024-4-22

[9]
How to fail with paired VNS therapy.

Brain Stimul. 2023

[10]
Importance of timing optimization for closed-loop applications of vagus nerve stimulation.

Bioelectron Med. 2023-4-27

本文引用的文献

[1]
Acute vagus nerve stimulation enhances reversal learning in rats.

Neurobiol Learn Mem. 2021-10

[2]
A Review of Parameter Settings for Invasive and Non-invasive Vagus Nerve Stimulation (VNS) Applied in Neurological and Psychiatric Disorders.

Front Neurosci. 2021-7-13

[3]
Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial.

Lancet. 2021-4-24

[4]
Vagus nerve stimulation enhances fear extinction as an inverted-U function of stimulation intensity.

Exp Neurol. 2021-7

[5]
Vagus nerve stimulation promotes extinction generalization across sensory modalities.

Neurobiol Learn Mem. 2021-5

[6]
Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve.

Nat Commun. 2021-3-9

[7]
Vagus nerve stimulation induces widespread cortical and behavioral activation.

Curr Biol. 2021-5-24

[8]
Use of a physiological reflex to standardize vagal nerve stimulation intensity improves data reproducibility in a memory extinction assay.

Brain Stimul. 2021

[9]
High intensity VNS disrupts VNS-mediated plasticity in motor cortex.

Brain Res. 2021-4-1

[10]
Single-neuron representation of learned complex sounds in the auditory cortex.

Nat Commun. 2020-8-31

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