Modeling microcircuits of realistic hippocampal neurons

模拟真实海马神经元的微电路

• 批准号: 6666811
• 负责人: NELSON P. SPRUSTON
• 金额: $ 20.4万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6666811
• 关键词: action potentials; cell morphology; computational neuroscience; computer simulation; dendrites; hippocampus; interneurons; laboratory rat; model design /development; neural information processing; neurons; neurophysiology; tissue /cell preparation; training

DESCRIPTION (provided by applicant): This project is a collaborative research program between experimental a cellular neurophysiologist and applied mathematicians. The central aim of the project is to develop detailed computational models of microcircuits composed principal neurons and interneurons in the CA1 region hippocampus. In particular, these computational models will: 1) Be based on the latest data available from patch-clamp experiments dealing with ionic conductances, calcium and two-photon imaging, and cell morphology. 2) Use ionic channel models specifically designed to accurately reproduce the experimentally determined behavior. 3) Use full-cell morphologies; in particular, the same individual cells from which electrophysiology data have been taken will be digitized for the computational studies. 4) Develop new adaptive computational methods that can be used to speed up the computational simulations. A long-term goal of the project is to develop sufficiently accurate models of excitatory and inhibitory cell types in the hippocampus so that realistic simulations of small networks present in the hippocampus can be performed. These computational simulations are intended to be a tool to guide the development of new patch-clamp experiments that further explore the functional behavior of the hippocampal region. It is anticipated that the resulting studies will ultimately foster an improved understanding of how the hippocampal network stores and retrieves memories. Specific benefits of the proposed research and training objectives are: 1) New models will be developed of morphologically reconstructed neurons from which electrophysiological measurements have been obtained using multiple patch-clamp electrodes and/or calcium imaging. 2) New ionic conductance models will be constructed to accurately reproduce the experimental results. 3) New computational methods will be developed to speed up the compartmental model simulations. 4) New models will be developed to explore network interactions between excitatory and inhibitory neurons within the hippocampus. 5) Graduate students and postdoctoral researchers, recruited from the ranks of applied mathematicians interested in biological applications, will be trained in computational neuroscience.

描述（由申请人提供）：该项目是实验细胞神经生理学家和应用数学家之间的合作研究项目。该项目的中心目标是开发由海马 CA1 区主要神经元和中间神经元组成的微电路的详细计算模型。特别是，这些计算模型将： 1）基于来自膜片钳实验的最新数据，涉及离子电导、钙和双光子成像以及细胞形态。 2) 使用专门设计的离子通道模型来准确再现实验确定的行为。 3）使用全细胞形态；特别是，已获取电生理学数据的相同单个细胞将被数字化以用于计算研究。 4）开发新的自适应计算方法，可用于加速计算模拟。 该项目的长期目标是开发海马体中兴奋性和抑制性细胞类型的足够准确的模型，以便可以对海马体中存在的小型网络进行真实模拟。这些计算模拟旨在成为指导新膜片钳实验开发的工具，进一步探索海马区域的功能行为。预计由此产生的研究最终将促进人们更好地了解海马网络如何存储和检索记忆。 拟议的研究和培训目标的具体好处是：1）将开发形态重建神经元的新模型，使用多个膜片钳电极和/或钙成像从中获得电生理测量。 2）将构建新的离子电导模型以准确再现实验结果。 3）将开发新的计算方法来加速隔室模型模拟。 4）将开发新模型来探索海马内兴奋性和抑制性神经元之间的网络相互作用。 5）从对生物应用感兴趣的应用数学家队伍中招募的研究生和博士后研究人员将接受计算神经科学方面的培训。