Biomedical Center, Faculty of Medicine in Pilsen, Charles University, , Prague, Czech Republic.
J Alzheimers Dis. 2024;101(1):259-276. doi: 10.3233/JAD-231386.
The hippocampal representation of space, formed by the collective activity of populations of place cells, is considered as a substrate of spatial memory. Alzheimer's disease (AD), a widespread severe neurodegenerative condition of multifactorial origin, typically exhibits spatial memory deficits among its early clinical signs before more severe cognitive impacts develop.
To investigate mechanisms of spatial memory impairment in a double transgenic rat model of AD.
In this study, we utilized 9-12-month-old double-transgenic TgF344-AD rats and age-matched controls to analyze the spatial coding properties of CA1 place cells. We characterized the spatial memory representation, assessed cells' spatial information content and direction-specific activity, and compared their population coding in familiar and novel conditions.
Our findings revealed that TgF344-AD animals exhibited lower precision in coding, as evidenced by reduced spatial information and larger receptive zones. This impairment was evident in maps representing novel environments. While controls instantly encoded directional context during their initial exposure to a novel environment, transgenics struggled to incorporate this information into the newly developed hippocampal spatial representation. This resulted in impairment in orthogonalization of stored activity patterns, an important feature directly related to episodic memory encoding capacity.
Overall, the results shed light on the nature of impairment at both the single-cell and population levels in the transgenic AD model. In addition to the observed spatial coding inaccuracy, the findings reveal a significantly impaired ability to adaptively modify and refine newly stored hippocampal memory patterns.
由位置细胞群体的集体活动形成的海马空间表示被认为是空间记忆的基础。阿尔茨海默病（AD）是一种广泛存在的、多因素起源的严重神经退行性疾病，通常在出现更严重的认知障碍之前，就表现出其早期临床特征中的空间记忆缺陷。
研究 AD 双转基因大鼠模型中空间记忆损伤的机制。
在这项研究中，我们使用了 9-12 月龄的双转基因 TgF344-AD 大鼠和年龄匹配的对照大鼠来分析 CA1 位置细胞的空间编码特性。我们对空间记忆的表现进行了特征分析，评估了细胞的空间信息含量和方向特异性活动，并比较了它们在熟悉和新颖环境中的群体编码。
我们的研究结果表明，TgF344-AD 动物在编码上的准确性较低，表现为空间信息减少和感受野增大。这种损伤在代表新环境的图谱中更为明显。当对照组在首次接触新环境时立即对方向上下文进行编码时，转基因动物则难以将这些信息纳入新形成的海马空间表示中。这导致存储的活动模式的正交化受损，这是与情景记忆编码能力直接相关的一个重要特征。
总体而言，这些结果揭示了在转基因 AD 模型中单细胞和群体水平上损伤的性质。除了观察到的空间编码不准确外，研究结果还表明，适应性地修改和完善新存储的海马记忆模式的能力显著受损。
