European Brain Research Institute (EBRI), Fondazione Rita Levi-Montalcini, Via Regina Elena 295, 00161, Rome, Italy.
Consiglio Nazionale delle Ricerche (CNR), Institute of Biochemistry and Cell Biology, Via E. Ramarini 32, 00015 Monterotondo, Rome, Italy.
Curr Alzheimer Res. 2020;17(3):259-268. doi: 10.2174/1567205017666200224122113.
Clinical evidence indicates that patients affected by Alzheimer's Disease (AD) fail to form new memories although their memories for old events are intact. This amnesic pattern depends on the selective vulnerability to AD-neurodegeneration of the hippocampus, the brain region that sustains the formation of new memories, while cortical regions that store remote memories are spared.
To identify the cellular mechanisms underlying impaired recent memories and intact remote memories in a mouse model of AD.
Glutamatergic synaptic currents were recorded by patch-clamp in acute hippocampal and anterior Cingulate Cortical (aCC) slices of AD-like Tg2576 mice and Wild-type (Wt) littermates subjected to the Contextual Fear Conditioning (CFC) task or in naïve conditions.
We identified a deficit in the formation of recent memories, but not in the recall of remote ones, in Tg2576 mice. With electrophysiological recordings, we detected CFC-induced modifications of the AMPA/NMDA ratio in CA1 pyramidal cells of Wt, but not Tg2576, mice one day after training. CFC-induced changes in the AMPA/NMDA ratio were also detected in the aCC of both Wt and Tg2576 mice 8 days after training.
Our data suggest that in the early AD stages synaptic plasticity of CA1 synapses, crucial to form new memories, is lost, while plasticity of aCC synapses is intact and contributes to the persistence of long-term memories.
临床证据表明，阿尔茨海默病（AD）患者尽管对旧事件的记忆完好，但无法形成新的记忆。这种遗忘模式取决于海马体对 AD 神经退行性变的选择性易损性，海马体是维持新记忆形成的大脑区域，而储存远程记忆的皮质区域则幸免。
在 AD 样 Tg2576 小鼠模型中，确定导致近期记忆受损而远程记忆完好的细胞机制。
通过在急性海马体和前扣带皮层（aCC）切片中进行膜片钳记录，研究 AD 样 Tg2576 小鼠和野生型（Wt）同窝仔鼠在进行情境恐惧条件反射（CFC）任务或在未训练条件下的谷氨酸能突触电流。
我们发现 Tg2576 小鼠在形成近期记忆方面存在缺陷，但在回忆远程记忆方面没有缺陷。通过电生理记录，我们在训练后一天检测到 Wt 但不是 Tg2576 小鼠 CA1 锥体神经元中 CFC 诱导的 AMPA/NMDA 比值的变化。在训练后 8 天，我们还在 Wt 和 Tg2576 小鼠的 aCC 中检测到 CFC 诱导的 AMPA/NMDA 比值的变化。
我们的数据表明，在 AD 的早期阶段，CA1 突触的突触可塑性丧失，这对形成新记忆至关重要，而 aCC 突触的可塑性完好无损，并有助于长期记忆的持续存在。
