Role of the neural cell adhesion molecule (NCAM) in amygdalo-hippocampal interactions and salience determination of contextual fear memory
Role of the neural cell adhesion molecule (NCAM) in amygdalo-hippocampal interactions and salience determination of contextual fear memory
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DOI：
10.1017/s1461145709991106
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发表时间：
2010-06-01
影响因子：
4.8
通讯作者：
Stork, Oliver
中科院分区：
文献类型：
--
作者：
Albrecht, Anne;Bergado-Acosta, Jorge Ricardo;Stork, Oliver
有证据表明，神经细胞粘附分子（NCAM）是中枢神经系统适应性和非适应性回路（重组）组织的重要分子组成部分。在这里，我们进一步研究了它在情境恐惧记忆形成过程中参与杏仁核和海马体功能的假设。通过激光捕获显微解剖和定量RT-PCR，我们发现杏仁核外侧和基底外侧亚核中NCAM mRNA的高表达水平，以及它们在恐惧记忆巩固过程中的训练强度和情境依赖性调节。此外，我们证明NCAM（-/-）小鼠在情境恐惧记忆中的缺陷可以通过情境预暴露来克服，即通过减少杏仁核对这种海马体依赖性记忆的调节影响。相反，NCAM（-/-）小鼠在显著过度训练后未能增加情境恐惧记忆，尽管它们充分增加了对听觉暗示的恐惧刺激的反应。最后，我们证明了NCAM - 1小鼠在恐惧记忆提取过程中杏仁核-海马theta同步减少。综上所述，这些结果表明ncam介导的细胞识别过程参与了杏仁核-海马系统的信息处理和杏仁核根据刺激显著性介导的情境恐惧记忆的调节。
Evidence suggests that the neural cell adhesion molecule (NCAM) is an important molecular constituent of adaptive and maladaptive circuit (re-)organization in the central nervous system. Here, we further investigate its putative involvement in amygdala and hippocampus functions during context fear memory formation. Using laser capture microdissection and quantitative RT-PCR, we show high NCAM mRNA expression levels in the lateral and basolateral subnuclei of the amygdala, as well as their training intensity- and context-dependent regulation during fear memory consolidation. Moreover, we demonstrate that deficits of NCAM(-/-) mice in context fear memory can he overcome through contextual pre-exposure, i.e. by reducing the modulatory influence of the amygdala on this hippocampus-dependent memory. On the contrary, NCAM(-/-) mice failed to increase contextual fear memory after salient over-training, although they adequately increased their response to auditory-cued fear stimuli. Finally, we demonstrate a reduction of amygdalo-hippocampal theta synchronization in NCAM l mice during fear memory retrieval. Together, these results suggest an involvement of NCAM-mediated cell recognition processes in information processing of the amygdalo-hippocampal system and in the amygdala-mediated modulation of context fear memory according to stimulus salience.