Cestari V, Costanzi M, Castellano C, Rossi-Arnaud C
Istituto di Neuroscienze del CNR, via del Fosso di Fiorano, 64-00143 Roma, Italy.
Neurobiol Learn Mem. 2006 Sep;86(2):133-43. doi: 10.1016/j.nlm.2006.01.003. Epub 2006 Feb 28.
Recent studies have shown that consolidated fear memories, when reactivated, return to a labile state that requires a new protein synthesis for reconsolidation. Post-retrieval infusion of an inhibitor of protein synthesis blocks memory reconsolidation processes. In a previous research, the role of MAPKs in memory consolidation has been shown in emotional tasks, such as passive and active avoidance. In particular, mice knockout for ERK1 had a better performance in comparison to wild type mice in both passive and active avoidance tasks. In the present study, in order to investigate the involvement of MAPKs in memory reconsolidation processes we administered immediately after retrieval, different doses of SL327 (an inhibitor of MEK, a kinase that activates both ERK1 and ERK2) both in C57BL/6 (C57) mice and ERK1 mutant mice tested in a fear conditioning task. Systemic administration of SL327 dose-dependently reduced the memory reconsolidation of fear memories in C57 mice. Moreover, SL327 administration impaired memory reconsolidation also in ERK1 mutant mice. Altogether, these results clearly indicate a central role for ERK2 protein in memory reconsolidation processes in mice.
最近的研究表明，巩固的恐惧记忆在重新激活时会恢复到不稳定状态，需要新的蛋白质合成来进行再巩固。检索后注入蛋白质合成抑制剂会阻断记忆再巩固过程。在先前的研究中，丝裂原活化蛋白激酶（MAPKs）在记忆巩固中的作用已在诸如被动和主动回避等情绪任务中得到证实。特别是，与野生型小鼠相比，ERK1基因敲除的小鼠在被动和主动回避任务中表现更好。在本研究中，为了研究MAPKs在记忆再巩固过程中的作用，我们在C57BL/6（C57）小鼠和在恐惧条件反射任务中测试的ERK1突变小鼠检索后立即给予不同剂量的SL327（一种MEK抑制剂，MEK是一种激活ERK1和ERK2的激酶）。全身给予SL327剂量依赖性地降低了C57小鼠恐惧记忆的再巩固。此外，给予SL327也损害了ERK1突变小鼠的记忆再巩固。总之，这些结果清楚地表明ERK2蛋白在小鼠记忆再巩固过程中起核心作用。
