There are evidences that the region of hippocampus is affected in the early stage of Alzheimer’s disease (AD). Moreover, the hippocampal pyramidal neurons receive cholinergic input from the medial septum. Thus, this study, based on the results of electrophysiological experiments, first constructs a modified hippocampal CA1 pyramidal neuronal model by introducing two new currents of M-current and calcium ion-activated potassium ion current to depict the cholinergic input receiving from the medial septum, and then explores how acetylcholine deficiency and beta-amyloid accumulation under the pathological condition of AD influence the neuronal dynamics in terms of theta band power and spiking frequency using computational approach. By simulating acetylcholine potentiated M-current and calcium ion-activated potassium ion current, numerical results reveal that the relative theta band power increases significantly and the firing rate decreases obviously when acetylcholine is deficient. Similarly, by simulating beta-amyloid enhanced delay rectification potassium ion current, we also detect that the relative theta band power increases as well as the firing rate decreases remarkably as beta-amyloid is accumulated. In addition, the mechanism underlying these dynamical changes in theta rhythm and firing behavior is investigated by nonlinear behavioral analysis, which demonstrates that both deficiency in acetylcholine and accumulation in beta-amyloid can promote the emergence of stable equilibrium state in this modified hippocampal neuronal model. Note that acetylcholine deficiency together with beta-amyloid deposition plays key role in the pathogenesis of AD. We expect these findings could have important implications on better understanding pathogenesis and expounding potential biomarkers for AD.

中文翻译：

---

与阿尔茨海默病相关的胆碱能作用海马神经元模型的动力学分析。


有证据表明海马区在阿尔茨海默病（AD）的早期阶段就受到影响。此外，海马锥体神经元接收来自内侧隔膜的胆碱能输入。因此，本研究在电生理实验结果的基础上，首先通过引入M电流和钙离子激活钾离子电流两种新电流，构建了改良的海马CA1锥体神经元模型，以描绘从内侧隔膜接收的胆碱能输入，然后利用计算方法探讨 AD 病理条件下乙酰胆碱缺乏和 β-淀粉样蛋白积累如何影响神经元动力学的 θ 带功率和尖峰频率。通过模拟乙酰胆碱增强的M电流和钙离子激活的钾离子电流，数值结果表明，当乙酰胆碱不足时，相对θ带功率显着增加，放电速率明显降低。类似地，通过模拟β-淀粉样蛋白增强延迟整流钾离子电流，我们还检测到随着β-淀粉样蛋白的积累，相对θ带功率增加，并且放电率显着降低。此外，通过非线性行为分析研究了θ节律和放电行为这些动态变化的机制，表明乙酰胆碱的缺乏和β-淀粉样蛋白的积累都可以促进这种改良的海马神经元模型中稳定平衡状态的出现。请注意，乙酰胆碱缺乏和 β-淀粉样蛋白沉积在 AD 的发病机制中起着关键作用。 我们预计这些发现可能对更好地理解 AD 的发病机制和阐明 AD 的潜在生物标志物产生重要影响。