NETWORK SIMULATION OF A LOCOMOTION NEURAL CIRCUIT

运动神经电路的网络仿真

• 批准号: 2246777
• 负责人: LEE E MOORE
• 金额: $ 15.18万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2246777
• 关键词: Agnatha; NMDA receptors; alternatives to animals in research; brain stem; chemical kinetics; chordate locomotion; computational neuroscience; electrophysiology; excitatory aminoacid; glutamates; interneurons; kainate; membrane channels; membrane potentials; motor neurons; neural information processing; neural inhibition; neural initiation; neuromuscular transmission; single cell analysis; spinal cord; synapses; voltage /patch clamp

The goal of this research is to implement a natural network model for locomotion in a primitive vertebrate, the lamprey, using measured membrane properties of neurons from the intact spinal cord to calculate post- synaptic potentials. We view the network model as a modifiable framework continually suggesting and being updated by new experiments for a better understanding of CNS behavior. The membrane properties will include the effects of the voltage dependent conductances and thus provide a means to evaluate their role in the integration of synaptic input of neurons that are part of the spinal cord neural circuitry involved in locomotion. The proposed transfer function approach is a unique way to determine the activation functions for neuronal units that incorporate the non-linear membrane properties of both soma and dendritic membranes. The voltage clamp data will be used to obtain Hodgkin-Huxley type voltage- dependent kinetic parameters that will be incorporated in a full scale non- linear differential equation for the computation of potential responses of each neuronal unit. Simulations of neurophysiological activity will be done with a neural circuit consisting of the principal interneuron types on each side of the spinal cord. The stimulations will be done using both the non-linear activation functions and synaptic weights on the dendritic compartments of the unit neurons. The following permutations of the basic network will be made: 1) a varying number of each of the cell types, 2) random and specific synaptic connections, 3) variation in specific membrane properties especially with regard to site densities. The stimulations will provide an evaluation of the effect of an unique type of synaptic receptor, namely the voltage dependent NMDA (N-methyl-D- aspartate) type, on network properties. The consequences of activation on network behavior of NMDA receptors on synaptic transfer are likely to be profound. The preliminary results show that NMDA induces a sharp tuning behavior which can greatly accentuate and filter the response of impinging synaptic inputs. The NMDA effects are strongly dependent on the membrane potential and will greatly affect the nature of neuronal interactions during network activity. The proposed network simulations provide an opportunity to assess the role of NMDA receptors in neural processing using a realistic neural rather than extrapolating from isolated or tissue cultured neurons.

本研究的目标是实现一个自然的网络模型， 运动在一个原始的脊椎动物，七鳃鳗，使用测量膜 完整脊髓神经元的特性来计算后 突触电位 我们将网络模型视为一个可修改的框架 不断地提出新的建议，并通过新的实验进行更新， 了解CNS行为。 膜的性质将包括 电压相关电导的影响，并因此提供了一种手段， 评估它们在神经元突触输入整合中的作用， 是参与运动的脊髓神经回路的一部分。 的 建议的传递函数方法是一种独特的方法来确定 神经元单元的激活函数， 索马和树突膜的膜特性。 电压钳数据将用于获得Hodgkin-Huxley型电压- 相关的动力学参数，将纳入一个全面的非- 线性微分方程计算的潜在的反应， 每个神经元单位 神经生理活动的模拟将是 用一个由主要的中间神经元类型组成的神经回路完成， 脊髓的每一侧刺激将使用 树突上的非线性激活函数和突触权重 单位神经元的间隔。 以下基本的排列 网络将被制成：1）不同数量的每种细胞类型，2） 随机和特定的突触连接，3）特定膜的变化 特别是关于站点密度的属性。 刺激将提供一个独特的类型的效果评估 突触受体，即电压依赖性NMDA（N-甲基-D- aspartate）类型，在网络属性上。 激活的后果 NMDA受体对突触传递的网络行为可能是 深刻 初步结果表明，NMDA诱导了一个尖锐的调谐 行为，可以大大加强和过滤的冲击响应 突触输入 NMDA的作用强烈依赖于细胞膜 潜在的，并将极大地影响神经元相互作用的性质 在网络活动中。 拟议的网络模拟提供了一个 机会来评估NMDA受体在神经处理中的作用， 一个真实的神经，而不是从孤立的或组织推断， 培养的神经元