Immune molecules, such as cytokines, complement, and major histocompatibility complex (MHC) proteins, in the central nervous system are often associated with neuropsychiatric disorders. Neuronal MHC class I (MHCI), such as H-2D, regulate neurite outgrowth, the establishment and function of cortical connections, and activity-dependent refinement in mice. We previously established mice expressing MHCI specifically in astrocytes of the media prefrontal cortex (mPFC) using the adeno-associated virus (AAV) vector under the control of the GfaABC1D promoter. Mice expressing the soluble form of H-2D (sH-2D) in the mPFC (sH-2D-expressing mice) showed abnormal behaviors, including social interaction deficits and cognitive dysfunctions. However, the pathophysiological significance of astroglial MHCI on higher brain functions, such as learning, memory, and behavioral flexibility, remains unclear. Therefore, cognitive function in mice expressing sH-2D in astrocytes of the mPFC was tested using the visual discrimination (VD) task. sH-2D-expressing mice were subjected to the VD and reversal learning tasks, and morphological analysis. In the pretraining, sH-2D-expressing mice required significantly more trials to reach the learning criterion than control mice. The total number of sessions, trials, normal trials, and correction trials to reach the VD criterion were also significantly higher in sH-2D-expressing mice than in control mice. A morphological study showed that dendritic complexity and spine density were significantly reduced in the dorsal striatum of sH-2D-expressing mice. Collectively, the present results suggest that the overexpression of astroglial MHCI in the mPFC results in impaired VD learning, which may be accompanied by decreased dendritic complexity in the dorsal striatum and mPFC.

中文翻译：

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内侧前额叶皮层星形胶质细胞主要组织相容性复合体 I 类的过度表达会损害小鼠的视觉辨别学习

中枢神经系统中的免疫分子，例如细胞因子、补体和主要组织相容性复合体 (MHC) 蛋白，通常与神经精神疾病有关。神经元 MHC I 类 (MHCI)，例如 H-2D，调节小鼠的神经突生长、皮质连接的建立和功能以及活动依赖性细化。我们之前使用 GfaABC1D 启动子控制下的腺相关病毒 (AAV) 载体在中层前额叶皮层 (mPFC) 的星形胶质细胞中建立了特异性表达 MHCI 的小鼠。在 mPFC 中表达可溶形式 H-2D (sH-2D) 的小鼠（表达 sH-2D 的小鼠）表现出异常行为，包括社交互动缺陷和认知功能障碍。然而，星形胶质细胞 MHCI 对高级脑功能的病理生理意义，如学习、记忆、和行为灵活性，仍不清楚。因此，使用视觉辨别 (VD) 任务测试了在 mPFC 星形胶质细胞中表达 sH-2D 的小鼠的认知功能。sH-2D 表达小鼠接受 VD 和逆转学习任务，以及形态分析。在预训练中，表达 sH-2D 的小鼠比对照小鼠需要更多的试验才能达到学习标准。在表达 sH-2D 的小鼠中，达到 VD 标准的会话、试验、正常试验和校正试验的总数也显着高于对照小鼠。形态学研究表明，表达 sH-2D 的小鼠背侧纹状体的树突复杂性和脊柱密度显着降低。总的来说，