Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy
Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy
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DOI：
10.1523/jneurosci.2151-15.2016
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发表时间：
2016-01-13
影响因子：
5.3
通讯作者：
Brown, Jonathan T.
中科院分区：
文献类型：
--
作者：
Booth, Clair A.;Witton, Jonathan;Brown, Jonathan T.
Tau蛋白聚集体的形成和沉积被认为是通过扰乱包括海马体在内的大脑区域的神经功能而导致痴呆症的认知障碍。我们在rTg4510转基因小鼠模型中使用了一组体内和体外的电生理记录，过度表达了人tau蛋白的突变形式，以研究tau病理对7-8月龄小鼠CA1区海马神经元功能的影响，在这一年龄点，rTg4510动物表现出晚期tau病理和进行性神经变性。体外记录显示，CA1锥体神经元的theta频率共振特性发生改变，Schaffer侧支突触的突触传递存在缺陷，突触的可塑性减弱和不平衡抑制。这些变化与CA1网络的异常振荡、锥体神经元的爆裂和体内的空间信息编码有关。我们的发现将细胞神经生理学中的倒立疗法相关的改变与行为依赖的网络功能改变联系起来。
The formation and deposition of tau protein aggregates is proposed to contribute to cognitive impairments in dementia by disrupting neuronal function in brain regions, including the hippocampus. We used a battery of in vivo and in vitro electrophysiological recordings in the rTg4510 transgenic mouse model, which overexpresses a mutant form of human tau protein, to investigate the effects of tau pathology on hippocampal neuronal function in area CA1 of 7- to 8-month-old mice, an age point at which rTg4510 animals exhibit advanced tau pathology and progressive neurodegeneration. In vitro recordings revealed shifted theta-frequency resonance properties of CA1 pyramidal neurons, deficits in synaptic transmission at Schaffer collateral synapses, and blunted plasticity and imbalanced inhibition at temporoammonic synapses. These changes were associated with aberrant CA1 network oscillations, pyramidal neuron bursting, and spatial information coding in vivo. Our findings relate tauopathy-associated changes in cellular neurophysiology to altered behavior-dependent network function.