Memory Erasure Experiments Indicate a Critical Role of CaMKII in Memory Storage.

Memory Erasure Experiments Indicate a Critical Role of CaMKII in Memory Storage.
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DOI:
10.1016/j.neuron.2017.09.010
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发表时间:
2017-09-27
期刊:
影响因子:
16.2
通讯作者:
Lisman J
Lisman J
中科院分区:
医学1区
文献类型:
--
作者:
Rossetti T;Banerjee S;Kim C;Leubner M;Lamar C;Gupta P;Lee B;Neve R;Lisman J

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大量的突触蛋白CaMK II是长时程增强(LTP)和记忆所必需的。然而,CaMKII是否仅在初始过程中需要,或者它是否也介导记忆存储仍然不清楚。对存储角色最直接的测试是擦除测试。在这个测试中,一个假定的记忆分子在学习后被短暂抑制。关键的预测是,这将产生持久的记忆擦除。我们使用海马中显性阴性CaMKII-α(K42 M)的瞬时病毒(HSV)表达进行了该测试。这就产生了持续的条件性位置回避的消除。作为额外的测试,我们发现激活的CaMKII(T286 D/T305 A/T306 A)的表达损害了位置回避,如果CaMKII以外的过程存储记忆,则不会出现预期的结果。我们的行为研究结果,与以前的实验LTP,强烈支持的关键作用,CaMKII在LTP的维护和记忆存储。Rossetti等人使用CaMKII的显性负性形式来消除依赖于大脑的行为记忆。与其他结果一起,新的发现有力地证明了记忆储存是由CaMKII介导的。
The abundant synaptic protein, CaMKII, is necessary for long-term potentiation (LTP) and memory. However, whether CaMKII is required only during initial processes or whether it also mediates memory storage remains unclear. The most direct test of a storage role is the erasure test. In this test, a putative memory molecule is transiently inhibited after learning. The key prediction is that this should produce persistent memory erasure. We conducted this test using transient viral (HSV) expression of dominant-negative CaMKII-alpha (K42M) in the hippocampus. This produced persistent erasure of conditioned place avoidance. As an additional test, we found that expression of activated CaMKII (T286D/T305A/T306A) impaired place avoidance, a result not expected if a process other than CaMKII stores memory. Our behavioral results, taken together with prior experiments on LTP, strongly support a critical role of CaMKII in LTP maintenance and memory storage. Rossetti et al. used a dominant-negative form of CaMKII to erase a hippocampal-dependent behavioral memory. Taken together with other results, the new findings make the strong case that memory storage is mediated by CaMKII.
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