Department of Psychiatry, Douglas Hospital Research Centre, McGill University, Montreal, QC H4H 1R3, Canada; Integrated Program in Neuroscience, McGill University, Montreal, QC H3A 0G4, Canada.
German Center for Neurodegenerative Diseases (DZNE), Magdeburg 39120, Germany; Leibniz Institute for Neurobiology (LIN), Magdeburg 39120, Germany.
Curr Biol. 2023 Jun 19;33(12):2425-2437.e5. doi: 10.1016/j.cub.2023.04.065. Epub 2023 May 22.
Converging evidence from human and rodent studies suggests that disrupted grid cell coding in the medial entorhinal cortex (MEC) underlies path integration behavioral deficits during early Alzheimer's disease (AD). However, grid cell firing relies on both self-motion cues and environmental features, and it remains unclear whether disrupted grid coding can account for specific path integration deficits reported during early AD. Here, we report in the J20 transgenic amyloid beta (Aβ) mouse model of early AD that grid cells were spatially unstable toward the center of the arena, had qualitatively different spatial components that aligned parallel to the borders of the environment, and exhibited impaired integration of distance traveled via reduced theta phase precession. Our results suggest that disrupted early AD grid coding reflects reduced integration of self-motion cues but not environmental information via geometric boundaries, providing evidence that grid cell impairments underlie path integration deficits during early AD.
来自人类和啮齿动物研究的综合证据表明，内侧内嗅皮层（MEC）中网格细胞编码的破坏是早期阿尔茨海默病（AD）期间路径整合行为缺陷的基础。然而，网格细胞的发射既依赖于自身运动线索，也依赖于环境特征，目前尚不清楚破坏的网格编码是否可以解释在早期 AD 期间报告的特定路径整合缺陷。在这里，我们在 J20 转基因淀粉样蛋白β（Aβ）AD 早期模型小鼠中报告，网格细胞在竞技场中心方向的空间不稳定，具有与环境边界平行排列的定性不同的空间成分，并表现出距离整合受损，表现为通过减少 θ 相位超前来减少。我们的研究结果表明，AD 早期网格编码的破坏反映了自身运动线索的整合减少，但不是通过几何边界的环境信息，为网格细胞损伤是 AD 早期路径整合缺陷的基础提供了证据。
