Wang Huimin, Feng Ruiben, Phillip Wang L, Li Fei, Cao Xiaohua, Tsien Joe Z
Brain and Behavior Discovery Institute, Medical College of Georgia, Augusta, Georgia 30912, USA.
Curr Biol. 2008 Oct 28;18(20):1546-54. doi: 10.1016/j.cub.2008.08.064. Epub 2008 Oct 16.
The labile state of short-term memory has been known for more than a century. It has been frequently reported that immediate postlearning intervention can readily disrupt newly formed memories. However, the molecular and cellular mechanisms underlying the labile state of new memory are not understood.
Using a bump-and-hole-based chemical-genetic method, we have rapidly and selectively manipulated alpha CaMKII activity levels in the mouse forebrain during various stages of the short-term memory processes. We find that a rapid shift in the alpha CaMKII activation status within the immediate 10 min after learning severely disrupts short-term memory formation. The same manipulation beyond the 15 min after learning has no effect, suggesting a critical time window for CaMKII action. We further show that during this same 10 min time window only, shifting in CaMKII activation state is capable of altering newly established synaptic weights and/or patterns.
The initial 10 min of memory formation and long-term potentiation are sensitive to inducible genetic upregulation of alphaCaMKII activity. Our results suggest that molecular dynamics of CaMKII play an important role in underlying synaptic labile state and representation of short-term memory during this critical time window.
短期记忆的不稳定状态已为人所知达一个多世纪。经常有报道称，学习后立即进行干预能够轻易扰乱新形成的记忆。然而，新记忆不稳定状态背后的分子和细胞机制尚不清楚。
利用基于凹凸法的化学遗传学方法，我们在短期记忆过程的不同阶段，对小鼠前脑α-CaMKII的活性水平进行了快速且选择性的调控。我们发现，学习后即刻10分钟内α-CaMKII激活状态的快速转变会严重扰乱短期记忆的形成。在学习后15分钟之后进行同样的操作则没有效果，这表明CaMKII发挥作用存在一个关键的时间窗口。我们进一步表明，仅在这相同的10分钟时间窗口内，CaMKII激活状态的转变能够改变新建立的突触权重和/或模式。
记忆形成和长时程增强的最初10分钟对α-CaMKII活性的可诱导基因上调敏感。我们的结果表明，在这个关键的时间窗口内，CaMKII的分子动力学在突触不稳定状态和短期记忆表征中起着重要作用。
