Department of Genetics & Molecular Neurobiology, Institute of Biology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
Int J Neuropsychopharmacol. 2010 Jun;13(5):661-74. doi: 10.1017/S1461145709991106. Epub 2009 Dec 14.
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 be 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 overtraining, although they adequately increased their response to auditory-cued fear stimuli. Finally, we demonstrate a reduction of amygdalo-hippocampal theta synchronization in NCAM-/- 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.
有证据表明，神经细胞黏附分子（NCAM）是中枢神经系统中适应性和失调性电路（再）组织的重要分子成分。在这里，我们进一步研究了它在杏仁核和海马体功能中的潜在作用，以形成情境恐惧记忆。使用激光捕获显微切割和定量 RT-PCR，我们显示了杏仁核外侧和基底外侧亚核中 NCAM mRNA 表达水平较高，以及在恐惧记忆巩固过程中它们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前暴露来克服，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无法增加情境恐惧记忆，尽管它们适当地增加了对听觉线索恐惧刺激的反应。最后，我们在 NCAM-/- 小鼠的恐惧记忆检索过程中观察到杏仁核-海马体θ同步的减少。总的来说，这些结果表明，NCAM 介导的细胞识别过程参与了杏仁核-海马体系统的信息处理，以及根据刺激显著性调节杏仁核介导的情境恐惧记忆。
