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）：该项目是实验性细胞神经生理学家和应用数学家之间的协作研究计划。该项目的核心目的是开发CA1区域海马组组成的主要神经元和中间神经元的微电路的详细计算模型。特别是，这些计算模型将：1）基于从贴片钳实验中获得的最新数据，该数据可用于离子电导，钙和两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，用于计算研究的相同单个细胞将数字化。 4）开发新的自适应计算方法，可用于加快计算模拟。 该项目的一个长期目标是在海马中开发足够准确的兴奋性和抑制性细胞类型模型，以便可以对海马中存在的小型网络进行现实模拟。这些计算模拟旨在指导开发新的贴片钳实验的工具，以进一步探索海马区域的功能行为。可以预料，最终的研究最终将促进人们对海马网络存储和检索记忆的方式的进一步了解。 拟议的研究和培训目标的具体好处是：1）将开发出形态重建神经元的新模型，使用多个贴片钳电极和/或钙成像从中获得了电生理测量。 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快隔室模型模拟。 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）将从对生物应用感兴趣的应用数学家的等级中招募的研究生和博士后研究人员将接受计算神经科学的培训。