Ohline Shane M, Liu Xinhuai, Ibrahim Mohamed F, Mockett Bruce M, Empson Ruth M, Abraham Wickliffe C, Iremonger Karl J, Jones Peter P
Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
HeartOtago, University of Otago, Dunedin, New Zealand.
Front Cell Neurosci. 2022 Aug 26;16:958876. doi: 10.3389/fncel.2022.958876. eCollection 2022.
Neuronal hyperexcitability in Alzheimer's disease (AD) models is thought to either contribute to the formation of amyloid beta plaques or result from their formation. Neuronal hyperexcitability has been shown in the cerebral cortex of the widely used young APPswe/PS1dE9 mice, which have accelerated plaque formation. However, it is currently unclear if hyperexcitability also occurs in CA1 hippocampal neurons of aged animals in this model. In the present work, we have compared intrinsic excitability and spontaneous synaptic inputs from CA1 pyramidal cells of 8-month-old APPswe/PS1dE9 and wildtype control mice. We find no change in intrinsic excitability or spontaneous postsynaptic currents (PSCs) between groups. We did, however, find a reduced input resistance and an increase in hyperpolarization-activated sag current. These results are consistent with findings from other aged AD model mice, including the widely used 5xFAD and 3xTg. Together these results suggest that neuronal hyperexcitability is not a consistent feature of all AD mouse models, particularly at advanced ages.
在阿尔茨海默病（AD）模型中，神经元的过度兴奋被认为要么促成β淀粉样蛋白斑的形成，要么是由其形成所致。在广泛使用的年轻APPswe/PS1dE9小鼠的大脑皮层中已显示出神经元过度兴奋，这些小鼠的斑块形成加速。然而，目前尚不清楚在该模型的老年动物的CA1海马神经元中是否也会出现过度兴奋。在本研究中，我们比较了8月龄APPswe/PS1dE9小鼠和野生型对照小鼠CA1锥体细胞的内在兴奋性和自发突触输入。我们发现两组之间的内在兴奋性或自发突触后电流（PSC）没有变化。然而，我们确实发现输入电阻降低，超极化激活的下陷电流增加。这些结果与其他老年AD模型小鼠（包括广泛使用的5xFAD和3xTg）的研究结果一致。这些结果共同表明，神经元过度兴奋并非所有AD小鼠模型的一致特征，尤其是在老年阶段。
