Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen, The Netherlands.
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
Stress. 2021 Mar;24(2):181-188. doi: 10.1080/10253890.2020.1747427. Epub 2020 Apr 11.
Extensive evidence indicates that noradrenergic activation is essentially involved in mediating the enhancing effects of emotional arousal on memory consolidation. Our current understanding of the neurobiological mechanisms underlying the memory-modulatory effects of the noradrenergic system is primarily based on pharmacological studies in rats, employing targeted administration of noradrenergic drugs into specific brain regions. However, the further delineation of the specific neural circuitry involved would benefit from experimental tools that are currently more readily available in mice. Previous studies have not, as yet, investigated the effect of noradrenergic enhancement of memory in mice, which show different cognitive abilities and higher endogenous arousal levels induced by a training experience compared to rats. In the present study, we investigated the effect of posttraining noradrenergic activation in male C57BL/6J mice on the consolidation of object recognition and object location memory. We found that the noradrenergic stimulant yohimbine (0.3 or 1.0 mg/kg) administered systemically immediately after an object training experience dose-dependently enhanced 24-h memory of both the identity and location of the object. Thus, these findings indicate that noradrenergic activation also enhances memory consolidation processes in mice, paving the way for a systematic investigation of the neural circuitry underlying these emotional arousal effects on memory. The current study successfully validated the effect of noradrenergic activation on both object recognition and object location memory in mice. This study thereby provides a fundamental proof-of-principle for the investigation of the neural circuitry underlying noradrenergic and arousal effects on long-term memory in mice.
大量证据表明,去甲肾上腺素能激活在介导情绪唤醒对记忆巩固的增强效应方面起着重要作用。我们目前对去甲肾上腺素系统对记忆调节作用的神经生物学机制的理解主要基于大鼠的药理学研究,通过向特定脑区靶向给予去甲肾上腺素药物来实现。然而,要进一步描绘涉及的特定神经回路,则需要借助于目前在小鼠中更容易获得的实验工具。先前的研究尚未在小鼠中研究去甲肾上腺素增强记忆的效果,与大鼠相比,小鼠表现出不同的认知能力和更高的内源性唤醒水平。在本研究中,我们研究了雄性 C57BL/6J 小鼠在训练后给予去甲肾上腺素激活对物体识别和物体位置记忆巩固的影响。我们发现,去甲肾上腺素兴奋剂育亨宾(0.3 或 1.0mg/kg)在物体训练后立即全身给药,可剂量依赖性地增强 24 小时内对物体身份和位置的记忆。因此,这些发现表明,去甲肾上腺素能激活也增强了小鼠的记忆巩固过程,为系统研究这些情绪唤醒对记忆的影响的神经回路奠定了基础。本研究成功验证了去甲肾上腺素能激活对小鼠物体识别和物体位置记忆的影响。因此,该研究为研究去甲肾上腺素能和唤醒对小鼠长期记忆的神经回路提供了基本的原理证明。