老化前额叶皮层中的髓质变质导致信号传输受损和工作记忆衰退:一项多规模计算研究
Sara Ibañez1,2, Nilapratim Sengupta1,3, Jennifer I Luebke1
1Department of Anatomy & Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA USA 02118.
bioRxiv : the preprint server for biology
|September 11, 2023
概括
衰老会改变大脑中的髓,影响认知功能. 计算模型表明,未完全修复的髓损伤会显著损害老年 rhesus 的空间工作记忆.
科学领域:
- 神经科学是一个神经科学.
- 计算生物学 计算生物学
- 认知科学 认知科学
背景情况:
- 正常的衰老会导致 rhesus 的背侧前额皮质 (dlPFC) 发生髓变化,这通常与认知能力下降有关.
- 复髓化在弥补髓降解中的作用,特别是与正在进行的降解相结合,在计算上仍然未被探索.
研究的目的:
- 以计算方式建模与年龄相关的髓变化对空间工作记忆的影响.
- 调查脱髓化和随后的复髓化如何影响神经元导电速度和动能传播.
主要方法:
- 根据子dlPFC数据开发了一种多分部的金字塔神经元模型,其中包含详细的轴突结构 (偏极点,对偏极点,内极点,紧接点).
- 利用拉索回归来确定影响轴突对髓变化敏感性的参数.
- 集成的单个神经元模型导致工作记忆的神经网络模型.
主要成果:
- 脱和复显著改变了导电速度,并在模拟的神经元中增加了动作潜力的故障.
- 完整的复髓化在很大程度上恢复了轴突传输和网络功能.
- 如果没有补偿,生物可信的髓损伤水平被预测会在衰老中导致显著的工作记忆障碍.
结论:
- 这项计算研究将电子显微镜的经验数据与衰老的行为结果联系起来.
- 与年龄相关的髓变化,特别是未补偿的髓损伤,在计算上被证明是工作记忆障碍的重要原因.
- 这些发现对了解多发性硬化症和精神分裂症等脱髓化疾病有意义.
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