Impairments in spatial representations and rhythmic coordination of place cells in the 3xTg mouse model of Alzheimer's disease
Impairments in spatial representations and rhythmic coordination of place cells in the 3xTg mouse model of Alzheimer's disease
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DOI：
10.1002/hipo.22697
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发表时间：
2017-04-01
期刊：
影响因子：
3.5
通讯作者：
Colgin, Laura Lee
中科院分区：
文献类型：
--
作者：
Mably, Alexandra J.;Gereke, Brian J.;Colgin, Laura Lee
阿尔茨海默病（Alzheimer's disease，AD）是一种不可逆的、高度进行性的神经退行性疾病。临床上，AD患者表现出情景记忆和空间记忆的障碍。然而，导致这些损伤的潜在神经元功能障碍仍然知之甚少。海马是至关重要的空间和情节记忆，因此，我们测试的假设，异常的神经元表示的空间海马有助于记忆缺陷在AD。为了验证这一假设，我们记录了尖峰从位置细胞在海马子区CA1，连同相应的节奏活动，在当地的场电位，在3xTg AD小鼠模型。我们观察到干扰的位置细胞放电模式，其中许多是一致的位置细胞干扰其他啮齿类动物模型的AD。我们发现，与对照小鼠相比，3xTg小鼠的空间定位细胞表达不稳定。此外，在3xTg小鼠中，海马节律引起的位置细胞放电的协调被破坏。具体来说，一个较小比例的位置细胞从3xTg小鼠显着相位锁定到θ和慢γ节律，和θ和慢γ阶段，尖峰发生也被改变。值得注意的是，这些干扰是在可检测的A病理学发展之前的年龄观察到的。这些发现之间的一致性在3xTg小鼠和以前的研究结果，从其他AD模型表明，干扰的地方细胞放电和海马节律与AD，而不是反映固有的特殊性，以特定的转基因模型。因此，紊乱的节奏组织的位置细胞活动可能有助于不稳定的空间表征，以及相关的空间记忆缺陷，在AD。(c)2017 Wiley Periodicals，Inc.
Alzheimer's disease (AD) is an irreversible and highly progressive neurodegenerative disease. Clinically, patients with AD display impairments in episodic and spatial memory. However, the underlying neuronal dysfunctions that result in these impairments remain poorly understood. The hippocampus is crucial for spatial and episodic memory, and thus we tested the hypothesis that abnormal neuronal representations of space in the hippocampus contribute to memory deficits in AD. To test this hypothesis, we recorded spikes from place cells in hippocampal subfield CA1, together with corresponding rhythmic activity in local field potentials, in the 3xTg AD mouse model. We observed disturbances in place cell firing patterns, many of which were consistent with place cell disturbances reported in other rodent models of AD. We found place cell representations of space to be unstable in 3xTg mice compared to control mice. Furthermore, coordination of place cell firing by hippocampal rhythms was disrupted in 3xTg mice. Specifically, a smaller proportion of place cells from 3xTg mice were significantly phase-locked to theta and slow gamma rhythms, and the theta and slow gamma phases at which spikes occurred were also altered. Remarkably, these disturbances were observed at an age before detectable A pathology had developed. Consistencies between these findings in 3xTg mice and previous findings from other AD models suggest that disturbances in place cell firing and hippocampal rhythms are related to AD rather than reflecting peculiarities inherent to a particular transgenic model. Thus, disturbed rhythmic organization of place cell activity may contribute to unstable spatial representations, and related spatial memory deficits, in AD. (c) 2017 Wiley Periodicals, Inc.