Reduced excitatory neuron activity and interneuron-type-specific deficits in a mouse model of Alzheimer's disease.
Reduced excitatory neuron activity and interneuron-type-specific deficits in a mouse model of Alzheimer's disease.
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DOI：
10.1038/s42003-022-04268-x
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发表时间：
2022-12-02
影响因子：
5.9
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中科院分区：
文献类型：
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阿尔茨海默病（Alzheimer's disease，AD）是一种以进行性记忆丧失和认知能力下降为特征的疾病。这些损害与AD患者神经元网络活动的早期改变相关。在淀粉样变性的小鼠模型中已经报道了单个神经元活性的破坏。然而，淀粉样蛋白病理学对不同神经元类型的自发活动的影响在体内仍然未被探索。在这里，我们使用在体内钙成像与多光子显微镜监测和比较的活动，兴奋性和两种类型的抑制性中间神经元在APP/PS1和对照小鼠异氟烷麻醉下的皮质。我们还确定了淀粉样蛋白积累和APP/PS1小鼠自发活动缺陷之间的关系。我们发现，生长抑素表达（SOM）的中间神经元是过度活跃的，而小白蛋白表达的中间神经元在APP/PS1小鼠是低活性的。只有SOM中间神经元过度活跃与接近淀粉样斑块。这些抑制缺陷伴随着APP/PS1小鼠兴奋性神经元活动的减少。我们的研究确定了淀粉样蛋白病理驱动的APP/PS1小鼠细胞特异性神经元放电缺陷。这些发现强调了解决神经元特异性缺陷的复杂性以改善阿尔茨海默病中的电路功能障碍的重要性。中间神经元特异性线显示，生长抑素中间神经元是过度活跃的，而锥体神经元和PV中间神经元是“低活性”的APP/PS1小鼠模型阿尔茨海默病。
Alzheimer’s disease (AD) is characterized by progressive memory loss and cognitive decline. These impairments correlate with early alterations in neuronal network activity in AD patients. Disruptions in the activity of individual neurons have been reported in mouse models of amyloidosis. However, the impact of amyloid pathology on the spontaneous activity of distinct neuronal types remains unexplored in vivo. Here we use in vivo calcium imaging with multiphoton microscopy to monitor and compare the activity of excitatory and two types of inhibitory interneurons in the cortices of APP/PS1 and control mice under isoflurane anesthesia. We also determine the relationship between amyloid accumulation and the deficits in spontaneous activity in APP/PS1 mice. We show that somatostatin-expressing (SOM) interneurons are hyperactive, while parvalbumin-expressing interneurons are hypoactive in APP/PS1 mice. Only SOM interneuron hyperactivity correlated with proximity to amyloid plaque. These inhibitory deficits were accompanied by decreased excitatory neuron activity in APP/PS1 mice. Our study identifies cell-specific neuronal firing deficits in APP/PS1 mice driven by amyloid pathology. These findings highlight the importance of addressing the complexity of neuron-specific deficits to ameliorate circuit dysfunction in Alzheimer’s disease. Interneuron-specific lines reveal that somatostatin interneurons are hyperactive whereas pyramidal neurons and PV interneurons are ‘hypoactive’ in the APP/PS1 mouse model of Alzheimer’s Disease.
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DOI：
10.1038/nrn3241
发表时间：
2012-05-18
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Buzsáki G;Anastassiou CA;Koch C
通讯作者：
Koch C
影响因子：
25
作者：
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Feng, Guoping
影响因子：
4.7
作者：
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通讯作者：
Stam, C. J.
影响因子：
9.8
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--
影响因子：
4.7
作者：
Kerrigan TL;Brown JT;Randall AD
通讯作者：
Randall AD