Patients with Alzheimer's disease (AD) suffer from spatial memory impairment and wandering behavior, but the brain circuit mechanisms causing such symptoms remain largely unclear. In healthy brains, spatially tuned hippocampal place cells and entorhinal grid cells exhibit distinct spike patterns in different environments, a circuit function called “remapping.” We tested remapping in amyloid precursor protein knockin (APP-KI) mice with impaired spatial memory. CA1 neurons, including place cells, showed disrupted remapping, although their spatial tuning was only mildly diminished. Medial entorhinal cortex (MEC) neurons severely lost their spatial tuning and grid cells were almost absent. Fast gamma oscillatory coupling between the MEC and CA1 was also impaired. Mild disruption of MEC grid cells emerged in younger APP-KI mice, although the spatial memory and CA1 remapping of the animals remained intact. These results point to remapping impairment in the hippocampus, possibly linked to grid cell disruption, as circuit mechanisms underlying spatial memory impairment in AD.

阿尔茨海默病 (AD) 患者患有空间记忆障碍和游荡行为，但导致此类症状的大脑回路机制仍不清楚。在健康的大脑中，经过空间调整的海马位置细胞和内嗅网格细胞在不同的环境中表现出不同的尖峰模式，这是一种称为“重新映射”的电路功能。我们在空间记忆受损的淀粉样前体蛋白敲入 (APP-KI) 小鼠中测试了重新映射。CA1 神经元，包括位置细胞，显示出被破坏的重新映射，尽管它们的空间调谐仅轻微减弱。内侧内嗅皮层 (MEC) 神经元严重失去了空间调谐，网格细胞几乎不存在。MEC 和 CA1 之间的快速伽马振荡耦合也受到损害。在年轻的 APP-KI 小鼠中出现了 MEC 网格细胞的轻度破坏，尽管动物的空间记忆和 CA1 重新映射保持不变。这些结果表明海马体的重新映射损伤，可能与网格细胞破坏有关，作为 AD 中空间记忆损伤的电路机制。