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语境学习增加了海马体小鼠神经元中的树突复杂性和 EphrinB2 水平。

Contextual learning increases dendrite complexity and EphrinB2 levels in hippocampal mouse neurons.

机构信息

Department of Psychology, Section of Neuroscience, University of Rome "Sapienza", via dei Marsi 78, 00185 Rome, Italy.

出版信息

Behav Brain Res. 2012 Feb 1;227(1):175-83. doi: 10.1016/j.bbr.2011.11.008. Epub 2011 Nov 15.

Abstract

Although the role of hippocampus in memory processing is well assessed, an association of experience-dependent behavioural modifications with hippocampal neuron morphological and biochemical changes deserves further characterisation. Here, we present evidence of dendritic alterations together with rapid accumulation of EphrinB2, a factor known to influence cell plasticity, in pyramidal neurons of the CA1 area of mouse hippocampus, during the formation of recent contextual fear memory. Male C57BL/6N mice exhibited a robust fear response 24h after contextual and cued fear conditioning. At this time and in the absence of the memory test, conditioned mice showed morphological alterations in hippocampal and lateral amygdala neurons. Western blot analysis of extracts from conditioned but not pseudoconditioned or naive mice showed a specific increase in the amount of EphrinB2 in the hippocampus but not the cortex. However, levels of EphA4 receptor, known to interact trans-synaptically with EphrinB2, did not change upon conditioning in extracts from the same structures. Finally, immunohistochemical analysis of the hippocampus and amygdala of conditioned mice showed increased levels of EphrinB2 in pyramidal neurons of the CA1 area, when compared to pseudoconditioned and control mice. Such increase was not observed in other hippocampal areas or the amygdala. These results suggest that rapid accumulation of EphrinB2 in hippocampal CA1 neurons is involved in the behavioural and cellular modifications induced by contextual fear conditioning. A similar mechanism does not appear to occur in lateral amygdala neurons, in spite of the robust behavioural and cellular modifications induced in such structure by cued fear conditioning.

摘要

虽然海马体在记忆处理中的作用已经得到很好的评估,但经验依赖性行为改变与海马体神经元形态和生化变化的关联值得进一步研究。在这里,我们提供了证据表明,在形成近期情境恐惧记忆期间,EphrinB2 这种已知影响细胞可塑性的因子在 CA1 区的锥体神经元中快速积累,同时伴随着树突的改变。在情境和线索恐惧条件作用后 24 小时,雄性 C57BL/6N 小鼠表现出强烈的恐惧反应。此时,在没有记忆测试的情况下,条件化小鼠表现出海马体和外侧杏仁核神经元的形态改变。Western blot 分析来自条件化而非伪条件化或未处理的小鼠的提取物显示,EphrinB2 的量在海马体中特异性增加,但在皮质中没有增加。然而,在来自相同结构的提取物中,与 EphrinB2 进行跨突触相互作用的 EphA4 受体的水平在条件化后没有变化。最后,对条件化小鼠的海马体和杏仁核进行免疫组织化学分析显示,与伪条件化和对照小鼠相比,CA1 区的锥体神经元中 EphrinB2 的水平增加。这种增加在其他海马体区域或杏仁核中没有观察到。这些结果表明,EphrinB2 在海马体 CA1 神经元中的快速积累参与了情境恐惧条件作用引起的行为和细胞改变。在外侧杏仁核神经元中似乎没有发生类似的机制,尽管在该结构中通过线索恐惧条件作用引起了强烈的行为和细胞改变。

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