Background:Abnormal morphology and function of neurons in the prefrontal cortex (PFC) are associated with cognitive deficits in rodent models of Alzheimer’s disease (AD), particularly in cortical layer-5 pyramidal neurons that integrate inputs from different sources and project outputs to corticalor subcortical structures. Pyramidal neurons in layer-5 of the PFC can be classified as two subtypes depending on the inducibility of prominent hyperpolarization-activated cation currents (h-current). However, the differences in the neurophysiological alterations between these two subtypes in rodent models of AD remain poorly understood. Objective:To investigate the neurophysiological alterations between two subtypes of pyramidal neurons in hAPP-J20 mice, a transgenic model for early onset AD. Methods:The synaptic transmission and intrinsic excitability of pyramidal neurons were investigated using whole-cell patch recordings. The morphological complexity of pyramidal neurons was detected by biocytin labelling and subsequent Sholl analysis. Results:We found reduced synaptic transmission and intrinsic excitability of the prominent h-current (PH) cells but not the non-PH cells in hAPP-J20 mice. Furthermore, the function of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels which mediated h-current was disrupted in the PH cells of hAPP-J20 mice. Sholl analysis revealed that PH cells had less dendritic intersections in hAPP-J20 mice comparing to control mice, implying that a lower morphological complexity might contribute to the reduced neuronal activity. Conclusion:These results suggest that the PH cells in the medial PFC may be more vulnerable to degeneration in hAPP-J20 mice and play a sustainable role in frontal dysfunction in AD.

中文翻译：

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阿尔茨海默病小鼠模型中内侧前额叶皮层中锥体神经元亚型的突触和内在兴奋性降低

背景：前额叶皮层 (PFC) 中神经元的异常形态和功能与阿尔茨海默病 (AD) 啮齿动物模型的认知缺陷有关，特别是在皮质第 5 层锥体神经元中，这些神经元整合了来自不同来源的输入并将输出投射到皮质或皮质下结构。PFC 第 5 层中的锥体神经元可根据突出的超极化激活阳离子电流 (h-current) 的诱导性分为两种亚型。然而，在 AD 啮齿动物模型中这两种亚型之间神经生理学改变的差异仍然知之甚少。目的：研究早发性AD转基因模型hAPP-J20小鼠锥体神经元两种亚型之间的神经生理学改变。方法：使用全细胞贴片记录研究了锥体神经元的突触传递和内在兴奋性。通过生物胞素标记和随后的 Sholl 分析检测锥体神经元的形态复杂性。结果：我们发现 hAPP-J20 小鼠中突出的 h 电流 (PH) 细胞而非非 PH 细胞的突触传递和内在兴奋性降低。此外，介导 h 电流的超极化激活环核苷酸门控 (HCN) 通道的功能在 hAPP-J20 小鼠的 PH 细胞中被破坏。Sholl 分析显示，与对照小鼠相比，hAPP-J20 小鼠中 PH 细胞的树突交叉较少，这意味着较低的形态复杂性可能导致神经元活动降低。结论：