Bach M E, Hawkins R D, Osman M, Kandel E R, Mayford M
Howard Hughes Medical Institute, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Cell. 1995 Jun 16;81(6):905-15. doi: 10.1016/0092-8674(95)90010-1.
We assessed hippocampal-dependent memory in mice with a Ca(2+)-independent form of CaMKII generated by the introduction of an aspartate at amino acid 286. The CaMKII-Asp-286 mice show normal LTP at high frequency stimulation, but in the 5-10 Hz range, they show a shift in the frequency-response curve favoring LTD. This range of frequencies is similar to the theta rhythm, which is associated with exploration in rodents. Using the Barnes maze to assess spatial memory, we found the transgenic mice could not learn to navigate to a specific location using spatial cues. In contrast, one line of transgenic mice performed normally in contextual fear conditioning, a task that is also hippocampal dependent. This dissociation between spatial and contextual memory suggests that even though both require the hippocampus, they may be mediated by different synaptic mechanisms.
我们通过在氨基酸286位引入天冬氨酸产生的一种不依赖Ca(2+)的CaMKII形式来评估小鼠海马依赖性记忆。CaMKII-Asp-286小鼠在高频刺激下表现出正常的长时程增强（LTP），但在5-10Hz范围内，它们的频率-反应曲线向有利于长时程抑制（LTD）的方向偏移。这个频率范围类似于theta节律，而theta节律与啮齿动物的探索行为相关。使用巴恩斯迷宫评估空间记忆，我们发现转基因小鼠无法利用空间线索学会导航到特定位置。相比之下，一组转基因小鼠在情境恐惧条件反射任务中表现正常，该任务同样依赖海马。空间记忆与情境记忆之间的这种分离表明，尽管两者都需要海马，但它们可能由不同的突触机制介导。
