长期以来，科学家一直在寻找记忆储存的分子基础，并试图寻找能存储记忆的分子，就像存储遗传信息的DNA一样。发表在近期的《神经科学杂志》（Journal of Neuroscience）上的文章中，来自Brandeis大学的科学家表示，他们首次发现了可以通过操控一种“记忆分子”——蛋白酶CaMKII在老鼠海马体中产生及消除记忆。
文章第一作者John Lisman表示：“研究记忆的核心问题是找到储存记忆的分子究竟是什么。这对于了解记忆本身以及相关疾病都是非常重要的。而在我们的研究中，确认了CaMKII是一种记忆分子。”
研究包括用电刺激神经突触来使其加强，这是一种长期增强过程（LTP），它是研究记忆的模型体系。CaMKII在LTP之后能持续的被激活，并增强突触传导，这些性质对于记忆分子而言是非常重要的。
就好像电脑中新信息存储一样，大脑中存储记忆的海马体分子的活动随着记忆的存储而改变。Lisman和同事证明，可以使记忆趋于饱和，但是在CaMKII受到化学影响，之前的记忆被去除之后。就又可以在突触之间插入新的记忆了。
这对于由记忆失去而引起的很多疾病都有着重要的意义，特别是对于突触过度活跃导致的癫痫症。研究显示，通过攻击记忆分子就可以使突触的活跃性减弱。
Lisman小组下一步计划研究CaMKII被攻击后发生了什么，利用带荧光的CaMKII，科学家就可以直接观察失去记忆的过程，之前研究显示当LTP发生时，CaMKII会移动到突触。
原始出处:
The Journal of Neuroscience, May 9, 2007, 27(19):5190-5199; doi:10.1523/JNEUROSCI.5049-06.2007
Reversal of Synaptic Memory by Ca2+/Calmodulin-Dependent Protein Kinase II Inhibitor
Magdalena Sanhueza,1 * Charmian C. McIntyre,2 * and John E. Lisman2
1Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, Santiago 780-0024, Chile, and 2Biology Department and Volen Center for Complex Systems–MS 008, Brandeis University, Waltham, Massachusetts 02454
Correspondence should be addressed to John E. Lisman, Biology Department and Volen Center for Complex Systems–MS 008, Brandeis University, 415 South Street, Waltham, MA 02454. Email: Lisman@brandeis.edu
Long-term potentiation (LTP) is an activity-dependent strengthening of synapses that is thought to underlie memory storage. Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been a leading candidate as a memory molecule because it is persistently activated after LTP induction and can enhance transmission. Furthermore, a mutation that blocks persistent activation blocks LTP and forms of learning. However, direct evidence for a role of the kinase in maintaining synaptic strength has been lacking. Here, we show that a newly developed noncompetitive inhibitor of CaMKII strongly reduces synaptic transmission in the CA1 region of the hippocampal slice. This occurs through both presynaptic and postsynaptic action. To study the role of CaMKII in the maintenance of LTP, inhibitor was applied after LTP induction and then removed. Inhibition occurred in both LTP and control pathways but only partially recovered. The nonrecovering component was attributable primarily to a postsynaptic change. To test whether nonrecovery was attributable to a persistent reversal of LTP, we first saturated LTP and then transiently applied inhibitor. This procedure allowed additional LTP to be induced, indicating a reversal of an LTP maintenance mechanism. This is the first procedure that can reverse LTP by chemical means and suggests that a component of synaptic memory is attributable to CaMKII. The procedure also enhanced the LTP that could be induced in the control pathway, consistent with the idea that CaMKII is involved in controlling basal synaptic strength, perhaps as a result of LTP that occurred in vivo.
Key words: CaMKII; depotentiation; hippocampus; LTP; maintenance; memory
