Imaging learned fear circuitry in awake mice using fMRI.
Imaging learned fear circuitry in awake mice using fMRI.
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DOI：
10.1111/ejn.12939
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Holmes MC
中科院分区：
文献类型：
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作者：
Harris AP;Lennen RJ;Marshall I;Jansen MA;Pernet CR;Brydges NM;Duguid IC;Holmes MC
功能性磁共振成像（fMRI）的学习行为在“清醒的啮齿动物”提供了转化临床前研究的药理学和遗传操作对大脑功能的影响的机会。功能磁共振成像最近被用来研究清醒大鼠的学习行为。在这里，这种方法被翻译到小鼠，使未来的功能磁共振成像研究可能会利用大量的转基因小鼠品系。一组小鼠被条件化以将闪光（条件刺激，CS）与足电击（PG;配对组）相关联，另一组小鼠接受足电击和明确未配对的闪光（UG;未配对组）。24小时后，使用fMRI在清醒小鼠中测量PG和UG对CS的响应的血氧水平依赖性信号（神经元激活的代理）。杏仁核，牵连在恐惧处理，被激活到更大程度上在PG比在UG中响应CS。此外，在UG中的延髓核被激活，以响应CS。由于CS在UG中发出不存在足部电击的信号，因此该区域可能涉及处理CS的安全方面。总之，首次使用功能磁共振成像可视化大脑激活清醒的小鼠正在完成一个学习的情感任务的报告。这项工作为未来的临床前功能磁共振成像研究铺平了道路，以研究遗传和环境对转基因小鼠疾病和衰老模型脑功能的影响。
Functional magnetic resonance imaging (fMRI) of learned behaviour in ‘awake rodents’ provides the opportunity for translational preclinical studies into the influence of pharmacological and genetic manipulations on brain function. fMRI has recently been employed to investigate learned behaviour in awake rats. Here, this methodology is translated to mice, so that future fMRI studies may exploit the vast number of genetically modified mouse lines that are available. One group of mice was conditioned to associate a flashing light (conditioned stimulus, CS) with foot shock (PG; paired group), and another group of mice received foot shock and flashing light explicitly unpaired (UG; unpaired group). The blood oxygen level‐dependent signal (proxy for neuronal activation) in response to the CS was measured 24 h later in awake mice from the PG and UG using fMRI. The amygdala, implicated in fear processing, was activated to a greater degree in the PG than in the UG in response to the CS. Additionally, the nucleus accumbens was activated in the UG in response to the CS. Because the CS signalled an absence of foot shock in the UG, it is possible that this region is involved in processing the safety aspect of the CS. To conclude, the first use of fMRI to visualise brain activation in awake mice that are completing a learned emotional task is reported. This work paves the way for future preclinical fMRI studies to investigate genetic and environmental influences on brain function in transgenic mouse models of disease and aging.