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不同恐惧消退延迟的小鼠在行为、应激和睡眠反应上的差异。

Differential behavioral, stress, and sleep responses in mice with different delays of fear extinction.

机构信息

Sleep Research Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA.

出版信息

Sleep. 2019 Oct 9;42(10). doi: 10.1093/sleep/zsz147.

DOI:10.1093/sleep/zsz147
PMID:31322681
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6783896/
Abstract

STUDY OBJECTIVES

Sleep, in particular rapid eye movement (REM), has been linked to fear learning and extinction; however, their relationship is poorly understood. We determined how different delays of extinction training (ET) impact fear-conditioned behaviors, changes in sleep, and stress responses.

METHODS

EEG activity, movement, and body temperature in mice were monitored via telemetry. Following contextual fear conditioning (shock training [ST]), separate groups of mice were reexposed to the context at 24-hour post-ST (24h ET-1) and at 48-hour post-ST (48h ET-1). Post-ET sleep amount and sleep-associated EEG (delta and theta) activity were compared to baseline and to post-ST sleep. Freezing, locomotion, grooming, and rearing were monitored to determine effects of ET on fear behaviors. Body temperature immediately after ET was monitored to assess stress-induced hyperthermia (SIH).

RESULTS

24h ET-1 and 48h ET-1 produced similar freezing and REM reductions, but dissimilar rearing activity and SIH. 24h ET-1 was followed by periods of suppressed REM-associated theta (REM-θ) activity, immediately after ET and during the subsequent dark period. Suppressed REM-θ was specific to sleep after 24h ET-1, and did not occur after ST, nor after 48h ET-1.

CONCLUSIONS

ET-1 at 24 and 48 hours after ST was associated with similar freezing and REM amounts, but with differences in other overt behaviors, in REM-θ, and in SIH. Freezing was not predictive of changes in other fear-associated responses. This study demonstrated that consideration of time delay from fear acquisition to extinction is important when assessing the relationships between extinction and behavior, sleep, and stress responses.

摘要

研究目的

睡眠,尤其是快速眼动(REM),与恐惧学习和遗忘有关;然而,它们之间的关系尚不清楚。我们确定了不同的遗忘训练(ET)延迟如何影响恐惧条件反射行为、睡眠变化和应激反应。

方法

通过遥测监测小鼠的脑电图活动、运动和体温。在情景恐惧条件反射(电击训练[ST])后,分别将小鼠在 ST 后 24 小时(24hET-1)和 ST 后 48 小时(48hET-1)重新暴露于环境中。将 ET 后的睡眠量和与睡眠相关的 EEG(δ 和θ)活动与基线和 ST 后的睡眠进行比较。通过监测冻结、运动、梳理和后肢站立来确定 ET 对恐惧行为的影响。ET 后立即监测体温以评估应激诱导性发热(SIH)。

结果

24hET-1 和 48hET-1 产生相似的冻结和 REM 减少,但不同的后肢站立活动和 SIH。24hET-1 后立即出现 REM 相关θ波(REM-θ)活动抑制,持续到 ET 后和随后的黑暗期。抑制 REM-θ 是 24hET-1 后睡眠的特异性,不会在 ST 后或 48hET-1 后发生。

结论

ST 后 24 和 48 小时的 ET-1 与相似的冻结和 REM 量相关,但与其他明显行为、REM-θ 和 SIH 不同。冻结并不能预测其他与恐惧相关的反应的变化。本研究表明,在评估遗忘与行为、睡眠和应激反应之间的关系时,考虑从恐惧获得到遗忘的时间延迟是很重要的。

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