Effects of a Spatial and Temporal Non-Uniform Extracellular Potential Distribution on the Activity of Single Neurones and Neuronal Populations

时空非均匀细胞外电位分布对单个神经元和神经元群活动的影响

• 批准号: EP/D066573/1
• 负责人: Costas Anastassiou
• 金额: $ 32.2万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FD066573%2F1
• 关键词: Effects; Spatial; Temporal; Non; Uniform

What impact have local electric field fluctuations on neuronal activity? Recording extracellular action potential is one of the primary methods to study brain function in the living animal. Understanding and quantifying the effect of the local field potential on the transmembrane potential of neurones is crucial for determining whether and when a given synaptic input will cause neurones to initiate an action potential. Since the days of Hodgkin-Huxley and their equations, neuronal membrane and extended dendritic as well as axonal structures have been modelled using one-dimensional cable theory in combination with linear or nonlinear time, voltage- and ligand-gated membrane conductances. In this entire body of work a common assumption was that the extracellular potential (Ve) is uniform, i.e. it does not depend on space, and is constant in time. Both assumptions, however, are known to be wrong - otherwise one could not record action potentials from outside neurones - but were justified by arguing that contributions of a non-uniform Ve(x, t) could be neglected. We propose to study theoretically the effect of a non-uniform and dynamic Ve on different levels of neuronal complexity: (a) on a single, unbranched cable model of a neurone, (b) on hippocampal pyramidal neurones with realistic dendritic morphology and electrophysiological signature and (c) on a population of simplified cortical cells exhibiting typical morphology and activity. In the first two stages, existing simulators from Prof. Christof Koch's lab (California Institute of Technology, USA) will be implemented as well as experimentally measured spatial and temporal Ve distributions from electrode arrays from Prof. Gyorgy Buzsaki's lab (Rutgers, USA). Recent in vitro studies indicate that in hippocampus electric field effects play a crucial role on neuronal synchronization. Based on these results, in the third stage, a reduced model will help us study the same effects on a neuronal population where features of small-world dynamics and synchronization will be investigated. All our theoretical conclusions will be compared to detailed experimental measurements.What effects do large excursions of Ve (up to 10 mV/mm for hippocampal sharp waves) have on the spiking activity of individual hippocampal pyramidal neurones? Will the firing of the neurone become entrained to the electric field through direct, so-called ephaptic, effects? How are these phenomena reflected upon a population of neurones firing? Are these effects manifested differently on the typical oscillatory frequencies that are attributed to diverse behavioural states? These are just a few of the questions we seek to investigate with this proposal.

局部电场波动对神经元活动有何影响？记录细胞外动作电位是研究活体动物脑功能的主要方法之一。了解和量化局部场电位对神经元跨膜电位的影响，对于确定给定的突触输入是否以及何时会导致神经元启动动作电位至关重要。自从Hodgkin-Huxley和他们的方程以来，神经元膜和扩展的树突以及轴突结构都是用一维电缆理论结合线性或非线性的时间、电压和配体门控的膜电导来模拟的。在这整个工作中，一个共同的假设是细胞外电位(Ve)是一致的，即它不依赖于空间，并且在时间上是恒定的。然而，这两个假设都被认为是错误的--否则人们无法记录来自外部神经元的动作电位--但通过论证非均匀Ve(x，t)的贡献可以被忽略，这两个假设是合理的。我们建议从理论上研究非均匀和动态的VE对不同程度的神经元复杂性的影响：(A)对神经元的单个未分支电缆模型的影响；(B)对具有真实树突形态和电生理特征的海马体锥体神经元的影响；以及(C)对表现出典型形态和活动的简化皮质细胞群的影响。在前两个阶段，将实施Christof Koch教授的实验室(美国加州理工学院)的现有模拟器，以及Gyorgy Buzsaki教授的实验室(美国罗格斯)的电极阵列的实验测量的空间和时间Ve分布。最近的体外研究表明，在海马区，电场效应对神经元的同步性起着至关重要的作用。基于这些结果，在第三阶段，一个简化的模型将帮助我们研究同样的对神经元种群的影响，其中将研究小世界动力学和同步的特征。我们所有的理论结论都将与详细的实验测量进行比较。Ve的大漂移(对于海马尖锐波，最高可达10 mV/mm)对单个海马锥体神经元的放电活动有什么影响？神经元的放电是否会通过直接的、所谓的触觉效应被带入电场？这些现象是如何反映在一群神经元上的呢？这些影响在归因于不同行为状态的典型振荡频率上表现得不同吗？这些只是我们试图通过这项提案调查的几个问题。