Role of left and right vagus nerves in linking peripheral adrenergic signals to contextual fear memory

IF 5.1 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-09-10 DOI:10.1016/j.lfs.2025.123946

João Munhoz , Ana Oliveira , Márcia Azevedo , Rafaela Seixas , Iara Rodrigues-de-Castro , Paula Serrão , Mónica Moreira-Rodrigues

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引用次数: 0

Abstract

Stress-induced physiological changes are crucial for adaptive responses to threats. Catecholamines, specifically epinephrine, activate peripheral β-adrenergic receptors, facilitating contextual fear memory consolidation. The vagus nerve is thought to be essential in transmitting physiological signals to the brain, influencing emotional memory consolidation. We aimed to evaluate the vagus nerve's role in contextual fear memory strengthening induced by epinephrine.

Male 129 × 1/SvJ mice underwent bilateral subdiaphragmatic vagotomy, right or left cervical vagotomy, or sham surgeries. After a seven-day recovery, mice were subjected to the fear conditioning paradigm, receiving three foot shocks on conditioning day, followed by contextual reminder exposure. Epinephrine (0.1 mg/kg, intraperitoneal, i.p.) was administered to a subset of left cervically vagotomized mice 3 min before each session. Freezing behavior was evaluated. Catecholamines were quantified by reverse-phase high-performance liquid chromatography (HPLC) with electrochemical detection.

Subdiaphragmatic vagotomy did not alter freezing behavior on both days. In cervical vagotomies, while no differences were observed on the conditioning day, a significant decrease in freezing behavior was observed on the context day. In left cervically vagotomized mice, epinephrine administration significantly increased freezing behavior.

In conclusion, unilateral left or right cervical vagotomy impaired contextual fear memory, contrary to subdiaphragmatic vagotomy. Impaired contextual fear memory in left cervical vagotomy was reversed by exogenous epinephrine, possibly due to the intact right cervical vagus. We suggest that stress-induced catecholamine release may activate thoracic peripheral β-adrenergic receptors and elevate systolic blood pressure, signals that are transmitted through the vagus nerve, influencing the hippocampus and facilitating contextual fear memory consolidation.

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左右迷走神经在连接周围肾上腺素能信号与情境恐惧记忆中的作用。

压力引起的生理变化对威胁的适应性反应至关重要。儿茶酚胺，特别是肾上腺素，激活外周β-肾上腺素能受体，促进情境恐惧记忆的巩固。迷走神经被认为是向大脑传递生理信号、影响情绪记忆巩固的关键。本研究旨在探讨迷走神经在肾上腺素诱导的情境恐惧记忆强化中的作用。雄性129 × 1/SvJ小鼠分别行双侧膈下迷走神经切断术、右侧或左侧颈部迷走神经切断术或假手术。恢复7天后，小鼠接受恐惧条件反射范式，在条件反射日接受三次足部电击，然后进行情境提醒暴露。肾上腺素（0.1 mg/kg，腹腔，i.p.）在每次疗程前3 分钟给予左颈部迷走神经切除小鼠亚组。评估了冻结行为。采用电化学反相高效液相色谱法测定儿茶酚胺含量。膈下迷走神经切开术并没有改变这两天的冰冻行为。在颈椎迷走神经切断术中，虽然在调节日没有观察到差异，但在情境日观察到冻结行为显著减少。在左侧颈部迷走神经切除的小鼠中，肾上腺素显著增加了冻结行为。结论：与膈下迷走神经切开术相反，单侧左或右颈迷走神经切开术会损害情境恐惧记忆。外源性肾上腺素可逆转左颈迷走神经切断后情境恐惧记忆受损，可能是由于右颈迷走神经完整所致。我们认为应激诱导的儿茶酚胺释放可能激活胸外周β-肾上腺素能受体并升高收缩压，这些信号通过迷走神经传递，影响海马并促进情境恐惧记忆的巩固。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.