Kishioka Ayumi, Fukushima Fumiaki, Ito Tamae, Kataoka Hirotaka, Mori Hisashi, Ikeda Toshio, Itohara Shigeyoshi, Sakimura Kenji, Mishina Masayoshi
Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
PLoS One. 2009;4(1):e4157. doi: 10.1371/journal.pone.0004157. Epub 2009 Jan 9.
Fear is one of the most potent emotional experiences and is an adaptive component of response to potentially threatening stimuli. On the other hand, too much or inappropriate fear accounts for many common psychiatric problems. Cumulative evidence suggests that the amygdala plays a central role in the acquisition, storage and expression of fear memory. Here, we developed an inducible striatal neuron ablation system in transgenic mice. The ablation of striatal neurons in the adult brain hardly affected the auditory fear learning under the standard condition in agreement with previous studies. When conditioned with a low-intensity unconditioned stimulus, however, the formation of long-term fear memory but not short-tem memory was impaired in striatal neuron-ablated mice. Consistently, the ablation of striatal neurons 24 h after conditioning with the low-intensity unconditioned stimulus, when the long-term fear memory was formed, diminished the retention of the long-term memory. Our results reveal a novel form of the auditory fear memory depending on striatal neurons at the low-intensity unconditioned stimulus.
恐惧是最强烈的情感体验之一，是对潜在威胁性刺激做出反应的一种适应性成分。另一方面，过度或不适当的恐惧是许多常见精神疾病的原因。越来越多的证据表明，杏仁核在恐惧记忆的获取、存储和表达中起着核心作用。在此，我们在转基因小鼠中开发了一种可诱导的纹状体神经元消融系统。与先前的研究一致，成年大脑中纹状体神经元的消融在标准条件下几乎不影响听觉恐惧学习。然而，当用低强度非条件刺激进行条件化时，纹状体神经元消融的小鼠中长期恐惧记忆的形成受到损害，而短期记忆不受影响。同样，在用低强度非条件刺激进行条件化24小时后，即长期恐惧记忆形成时，纹状体神经元的消融会减少长期记忆的保留。我们的结果揭示了一种在低强度非条件刺激下依赖于纹状体神经元的新型听觉恐惧记忆形式。
