Maguschak Kimberly A, Ressler Kerry J
Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Howard Hughes Medical Institute, Emory University, Atlanta, Georgia 30329, USA.
Nat Neurosci. 2008 Nov;11(11):1319-26. doi: 10.1038/nn.2198. Epub 2008 Sep 28.
beta-catenin has been implicated in neuronal synapse regulation and remodeling. Here we have examined beta-catenin expression in the adult mouse brain and its role in amygdala-dependent learning and memory. We found alterations in beta-catenin mRNA and protein phosphorylation during fear-memory consolidation. Such alterations correlated with a change in the association of beta-catenin with cadherin. Pharmacologically, this consolidation was enhanced by lithium-mediated facilitation of beta-catenin. Genetically, the role of beta-catenin was confirmed with site-specific deletions of loxP-flanked Ctnnb1 (encoding beta-catenin) in the amygdala. Baseline locomotion, anxiety-related behaviors and acquisition or expression of conditioned fear were normal. However, amygdala-specific deletion of Ctnnb1 prevented the normal transfer of newly formed fear learning into long-term memory. Thus, beta-catenin may be required in the amygdala for the normal consolidation, but not acquisition, of fear memory. This suggests a general role for beta-catenin in the synaptic remodeling and stabilization underlying long-term memory in adults.
β-连环蛋白与神经元突触调节和重塑有关。在此，我们研究了成年小鼠大脑中β-连环蛋白的表达及其在杏仁核依赖性学习和记忆中的作用。我们发现，在恐惧记忆巩固过程中，β-连环蛋白的mRNA和蛋白磷酸化发生了改变。这种改变与β-连环蛋白与钙黏蛋白结合的变化相关。在药理学上，锂介导的β-连环蛋白促进作用增强了这种巩固。在遗传学上，通过在杏仁核中对loxP侧翼的Ctnnb1（编码β-连环蛋白）进行位点特异性缺失，证实了β-连环蛋白的作用。基线运动、焦虑相关行为以及条件性恐惧的习得或表达均正常。然而，杏仁核特异性缺失Ctnnb1会阻止新形成的恐惧学习正常转化为长期记忆。因此，杏仁核中正常巩固恐惧记忆可能需要β-连环蛋白，但不需要其参与恐惧记忆的习得。这表明β-连环蛋白在成体长期记忆的突触重塑和稳定中具有普遍作用。
