In Alzheimer’s disease (AD), hippocampus-dependent memories underlie an extensive decline. The neuronal ensemble encoding a memory, termed engram, is partially recapitulated during memory recall. Artificial activation of an engram can restore memory in a mouse model of early AD, but its fate and the factors that render the engram nonfunctional are yet to be revealed. Here, we used repeated two-photon in vivo imaging to analyze fosGFP transgenic mice (which express enhanced GFP under the Fos promoter) performing a hippocampus-dependent memory task. We found that partial reactivation of the CA1 engram during recall is preserved under AD-like conditions. However, we identified a novelty-like ensemble that interfered with the engram and thus compromised recall. Mimicking a novelty-like ensemble in healthy mice was sufficient to affect memory recall. In turn, reducing the novelty-like signal rescued the recall impairment under AD-like conditions. These findings suggest a novel mechanistic process that contributes to the deterioration of memories in AD.

在阿尔茨海默氏病（AD）中，海马依赖性记忆是广泛下降的基础。记忆记忆期间，编码记忆的神经元整体被部分概括。字母的人工激活可以恢复早期AD小鼠模型的记忆，但其命运和使字母失去功能的因素尚待揭示。在这里，我们使用重复的两光子体内成像来分析fosGFP转基因小鼠（在Fos下表达增强的GFP启动子）执行海马依赖性记忆任务。我们发现召回期间CA1字母的部分重新激活在类似AD的条件下得以保留。但是，我们发现了一个类似新颖的合奏，该合奏会干扰印章，从而影响回忆。在健康小鼠中模仿新颖的合奏足以影响记忆回忆。反过来，减少类似新颖性的信号可以挽救类似AD的情况下的召回障碍。这些发现暗示了一种新颖的机制过程，其有助于AD中记忆的恶化。