Endogenous inhibition of CaMKII: A Novel molecular mechanism to terminate memory formation

在大脑中制造和存储记忆需要什么机制？这些机制仍然没有得到充分的理解，这一事实阻碍了我们治愈智力低下等疾病中的学习和记忆缺陷。我的实验室正在研究小鼠学习和记忆的基础机制。我们用小鼠进行研究，因为在人类中，我们不能进行建立机制所需的明确定义的实验操作，而小鼠是最接近人类的动物物种，已经为其建立了非常大的复杂操作体系。我们和其他人已经证明，一种名为CaMKII的酶是制造记忆所必需的，但不是存储记忆所必需的。为了终止记忆的产生，需要关闭酶。我们已经提出了一种内源性抑制蛋白(CaMKIINpha)来执行这一功能。需要更多的研究来验证我们的假设，在这里，我们建议进行这样的研究。如果我们的假设是正确的，那么后续研究将检验新的记忆机制是否会在与记忆缺陷相关的疾病中受损。

What mechanisms are needed to make and store memories in the brain? These mechanisms are still not sufficiently well understood, a fact that prevents us from curing learning and memory deficits in diseases such as mental retardation. My laboratory is studying mechanisms that underlie learning and memory in mice. We perform studies with mice, because in humans we cannot perform well-defined experimental manipulations that are needed to establish mechanisms, and mice are the closest animal species to humans for which a very large repertoire of sophisticated manipulations has been established. We and others have shown that an enzyme called CaMKII is required for the making, but not for the storage, of memory. To terminate the memory making the enzyme needs to be switched off. We have proposed that an endogenous inhibitor protein (CaMKIINalpha) performs this function. More studies are required to validate our hypothesis and here we propose to carry out such studies. If our hypothesis were correct, then follow-up studies will examine whether the novel memory mechanism could be impaired in diseases with associated memory deficits.