COMPUTER METHODS FOR PHYSIOLOGICAL PROBLEMS

在整个赠款期间，我们使用计算机模拟， 深入了解形态和离子的相对贡献 单个神经细胞功能的通道。我们已经开发出一种 程序，神经元，（可在PC和Unix工作站），以模拟 具有复杂分支形态的神经元个体和网络， 渠道类型多，渠道分布不均匀，渠道受限 细胞外间隙它的一个很好的例子是在解释 动作电位的失效和恢复的实验结果 由于部分脱髓鞘和新节点的形成， 多发性硬化 我们计划在年继续改进我们现有的计算机软件。 为了使神经细胞模拟的任务不那么令人生畏， 非专家在数值方法-和更少的解释， 复杂的建模者经常发现一个小而新颖的要求 需要在计算机编程上进行重大且不可预见的投资。的 神经元模拟软件将在几个方向上扩展， 最重要的是：（1）增加数值方法的鲁棒性， 存在变化的离子浓度， 扩散(2)增加了新图形界面的功能， 管理和维护对复杂模拟的概念控制。 (3)增加兼容性（通过使用过滤器）与其他 模拟程序，以促进共享，重用，验证， 建立在彼此的模拟之上。(4)大大增加了杠杆作用， 通过利用互操作性协议（CORBA）， 将允许在其他分析包中嵌入NEURON组件 (and反之亦然）。 我们计划使用NEURON程序对以下模型进行模拟： 程式化的神经元和突触传递模型。 由于首席研究员搬到耶鲁大学， 与一些使用NEURON来建模的实验家有着更密切的联系， 他们的系统。由此产生的个人合作将提高这些 研究人员对神经元的使用，并反馈到改善神经元的方法 作为一种实用的研究工具。

Throughout the period of this grant we have used computer simulations to gain insight into the relative contributions of morphology and ionic channels to the functioning of single nerve cells. We have developed a program, NEURON, (available on PC's and Unix workstations) to simulate individual and networks of neurons with complex branching morphology, multiple channel types, inhomogeneous channel distribution, and restricted extracellular space. A good example of its use is in the interpretation of experimental results on failure and recovery of action potential propagation due to partial demyelination and new node formation in multiple sclerosis. We plan to continue the refinement of our present computer software in order to make the task of nerve cell simulation much less intimidating for non-specialists in numerical methods - and much less infuriating to sophisticated modelers who too often find that a small but novel request requires a serious and unforeseen investment in computer programming. The neuron simulation software will be extended in several directions, the most important ones being: (1) Increased numerical method robustness in the presence of changing ionic concentration including longitudinal diffusion. (2) Increased functionality of the new graphical interface for management of and maintaining conceptual control over complex simulations. (3) Increased compatibility (through the use of filters) with other simulation programs to promote sharing, reuse, verification of, and building upon each others simulations. (4) Vastly increased leveraging of the power of NEURON by utilizing an interoperability protocol (CORBA) that will allow embedding of NEURON components within other analysis packages (and vice versa) in a distributed fashion across a network. We plan to use the NEURON program to carry out simulations on models of stylized neurons and models of synaptic transmission. As a consequence of the principal investigator's move to Yale there will be much closer ties to some of the experimentalists using NEURON to model their systems. The resulting personal collaborations will enhance those researcher's usage of NEURON and feed back into ways of improving NEURON's effectiveness as a practical research tool.