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首页> 外文期刊>Journal of Computational Neuroscience >Beta-amyloid induced changes in A-type K~+ current can alter hippocampo-septal network dynamics
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Beta-amyloid induced changes in A-type K~+ current can alter hippocampo-septal network dynamics

机译：β-淀粉样蛋白诱导的A型K〜+电流变化可改变海马-前房间隔网络的动力学

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摘要

Alzheimer's disease (AD) progression is usually associated with memory deficits and cognitive decline. A hallmark of AD is the accumulation of beta-amyloid (Aβ) peptide, which is known to affect the hippocampal pyramidal neurons in the early stage of AD. Previous studies have shown that A(β can block A-type K~+ currents in the hippocampal pyramidal neurons and enhance the neuronal excitability. However, the mechanisms underlying such changes and the effects of the hyper-excited pyramidal neurons on the hippocampo-septal network dynamics are still to be investigated. In this paper, Aβ-blocked A-type current is simulated, and the resulting neuronal and network dynamical changes are evaluated in terms of the theta band power. The simulation results demonstrate an initial slight but significant theta band power increase as the A-type current starts to decrease. However, the theta band power eventually decreases as the A-type current is further decreased. Our analysis demonstrates that Aβ blocked A-type currents can increase the pyramidal neuronal excitability by preventing the emergence of a steady state. The increased theta band power is due to more pyramidal neurons recruited into spiking mode during the peak of pyramidal theta oscillations. However, the decreased theta band power is caused by the spiking phase relationship between different neuronal populations, which is critical for theta oscillation, is violated by the hyper-excited pyramidal neurons. Our findings could provide potential implications on some AD symptoms, such as memory deficits and AD caused epilepsy.
机译：阿尔茨海默氏病（AD）的进展通常与记忆力减退和认知能力下降有关。 AD的标志是β-淀粉样蛋白（Aβ）肽的积累，已知它会在AD早期影响海马锥体神经元。先前的研究表明，A（β可以阻断海马锥体神经元中的A型K〜+电流并增强神经元兴奋性，但是，这种改变的机制以及高兴奋性锥体神经元对海马间隔的影响网络动力学还有待研究，本文模拟了Aβ阻断的A型电流，并根据θ带功率评估了神经元和网络动力学变化，仿真结果表明初始的轻微但重要的θ随着A型电流开始减小，带电功率增加，但θ带功率最终随着A型电流的进一步减小而减小，我们的分析表明，Aβ阻断A型电流可通过防止神经元兴奋性增加锥体神经元兴奋性。 θ谱带功率的增加是由于在金字塔形θ振荡峰值期间更多的锥体神经元被募集为突波模式继续但是，θ带功率的降低是由不同神经元种群之间的尖峰相位关系引起的，这对θ振荡至关重要，而过度兴奋的锥体神经元则违反了这一关系。我们的发现可能对某些AD症状（如记忆力减退和AD引起的癫痫）提供潜在的影响。

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