長(zhǎng)期以來(lái)，科學(xué)家一直在尋找記憶儲(chǔ)存的分子基礎(chǔ)，并試圖尋找能存儲(chǔ)記憶的分子，就像存儲(chǔ)遺傳信息的DNA一樣,。發(fā)表在近期的《神經(jīng)科學(xué)雜志》（Journal of Neuroscience）上的文章中，來(lái)自Brandeis大學(xué)的科學(xué)家表示,，他們首次發(fā)現(xiàn)了可以通過(guò)操控一種“記憶分子”——蛋白酶CaMKII在老鼠海馬體中產(chǎn)生及消除記憶,。
文章第一作者John Lisman表示：“研究記憶的核心問(wèn)題是找到儲(chǔ)存記憶的分子究竟是什么。這對(duì)于了解記憶本身以及相關(guān)疾病都是非常重要的,。而在我們的研究中,，確認(rèn)了CaMKII是一種記憶分子。”
研究包括用電刺激神經(jīng)突觸來(lái)使其加強(qiáng),，這是一種長(zhǎng)期增強(qiáng)過(guò)程（LTP）,，它是研究記憶的模型體系。CaMKII在LTP之后能持續(xù)的被激活,，并增強(qiáng)突觸傳導(dǎo),，這些性質(zhì)對(duì)于記憶分子而言是非常重要的。
就好像電腦中新信息存儲(chǔ)一樣,，大腦中存儲(chǔ)記憶的海馬體分子的活動(dòng)隨著記憶的存儲(chǔ)而改變,。Lisman和同事證明,，可以使記憶趨于飽和，但是在CaMKII受到化學(xué)影響,，之前的記憶被去除之后。就又可以在突觸之間插入新的記憶了,。
這對(duì)于由記憶失去而引起的很多疾病都有著重要的意義,，特別是對(duì)于突觸過(guò)度活躍導(dǎo)致的癲癇癥。研究顯示,，通過(guò)攻擊記憶分子就可以使突觸的活躍性減弱,。
Lisman小組下一步計(jì)劃研究CaMKII被攻擊后發(fā)生了什么，利用帶熒光的CaMKII,，科學(xué)家就可以直接觀察失去記憶的過(guò)程,，之前研究顯示當(dāng)LTP發(fā)生時(shí)，CaMKII會(huì)移動(dòng)到突觸,。
原始出處:
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: [email protected]
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
