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阿尔茨海默病转基因动物认知地图损伤的细胞-网络机制

郑丽^1,2, 王玲^1,3,2, 杨佳佳^1,3,2, 郑晨光^1,3,2,*

¹天津大学精密仪器与光电子工程学院，天津 300072；²天津市脑科学与神经工程重点实验室，天津 300072；³天津大学医学工程与转化医学研究院，天津 300072

摘要

阿尔茨海默病(Alzheimer's disease, AD)是一种典型的认知障碍疾病，且发病率逐年增加，是当今老龄化社会中老年人失能和死亡的主要原因之一。AD最典型的症状之一是空间记忆障碍，它发生于60%以上的患者人群中，这种记忆障碍与脑内认知地图的损伤密切相关。大脑中内嗅皮层网格细胞(grid cells)和海马位置细胞(place cells)是空间记忆和导航功能的重要细胞基础，探究并阐明AD转基因啮齿动物中此类细胞的异常放电模式，以及脑电节律协调神经元放电的损伤机制，对揭示AD功能缺陷及诊疗靶点至关重要。本文综述了近年来基于AD转基因啮齿动物模型的神经活动研究，着重阐述内嗅皮层和海马神经元放电特征的改变以及脑电节律的异常，梳理AD所致空间记忆障碍的潜在细胞-网络机制，为今后AD的诊疗提供科学依据。

关键词： 阿尔茨海默病; 海马; 内嗅皮层; 位置细胞; 空间记忆

Impaired cognitive map in transgenic animals relevant to Alzheimer's disease: from neurons to network 

ZHENG Li^1,2, WANG Ling^1,3,2, YANG Jia-Jia^1,3,2, ZHENG Chen-Guang^1,3,2,*

¹School of Precision Instrument and Opto-Electronics Engineering, Tianjin University, Tianjin 300072, China；²Tianjin Key Laboratory of Brain Science and Neuroengineering, Tianjin 300072, China；³Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China

Abstract

Alzheimer's disease (AD) is a typical cognitive disorder with an increasing incidence in recent years. AD is also one of the main causes of disability and death of the elderly in current aging society. One of the most common symptoms of AD is spatial memory impairment, which occurs in more than 60% of patients. This memory loss is closely related to the impairment of cognitive maps in the brain. The entorhinal grid cells and the hippocampal place cells are important cellular basis for spatial memory and navigation functions in the brain. Understanding the abnormal firing pattern of these neurons and their impaired coordination to neural oscillations in transgenic rodents is crucial for identifying the therapeutic targets for AD. In this article, we review recent studies on neural activity based on transgenic rodent models of AD, with a focus on the changes in the firing characteristics of neurons and the abnormal electroencephalogram (EEG) rhythm in the entorhinal cortex and hippocampus. We also discuss potential cell-network mechanism of spatial memory disorders caused by AD, so as to provide a scientific basis for the diagnosis and treatment of AD in the future.

Key words: Alzheimer’s disease; hippocampus; entorhinal cortex; place cells; spatial memory

收稿日期：　　录用日期：

通讯作者：郑晨光　　E-mail: cgzheng@tju.edu.cn

DOI: 10.13294/j.aps.2023.0054

引用本文：

郑丽, 王玲, 杨佳佳, 郑晨光. 阿尔茨海默病转基因动物认知地图损伤的细胞-网络机制[J]. 生理学报 2023; 75 (5): 671-681.

ZHENG Li, WANG Ling, YANG Jia-Jia, ZHENG Chen-Guang. Impaired cognitive map in transgenic animals relevant to Alzheimer's disease: from neurons to network . Acta Physiol Sin 2023; 75 (5): 671-681 (in Chinese with English abstract).