COMPUTATION AND SYNAPTIC MODIFICATION IN THE DENTATE

齿状体中的计算和突触修改

• 批准号: 2250346
• 负责人: WILLIAM R HOLMES
• 金额: $ 9.51万
• 依托单位: OHIO UNIVERSITY ATHENS
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2250346
• 关键词: alternatives to animals in research; calcium flux; computational neuroscience; dentate gyrus; granule cell; long term potentiation; model design /development; synapses

The long-term goal of this research is to understand the function of the hippocampus. The hippocampus is thought to play an important role in learning and memory functions and is involved in a number of major neurological disorders. If we are to understand hippocampal function, we must understand how computation and synaptic modification take place in the cells of the hippocampus. Computer modeling is a new and powerful tool for studying hippocampal function. Computer models of individual neurons can he used to test hypotheses difficult to address experimentally and can provide specific predictions about the mechanisms of observed phenomena. In this research highly detailed models of hippocampal dentate granule cells will be developed. These models will include complete morphology along with mathematical descriptions of synaptic and non-synaptic conductances and of processes that control calcium concentration in the cell. Models will be made as realistic as possible to be consistent with the considerable body of experimental data available. These highly detailed models will be used to: 1) Assess the importance of the morphological and electrotonic structure for the function of dentate granule cells. 2) Determine the range of computational possibilities of these cells given their complement of ion channel types, distributions and densities. How the computational possibilities change when certain parameter values change might reveal phenomena seen with certain pathological conditions. 3) Explain how calcium concentration changes in the cell might be correlated with the induction of long-term potentiation (LTP) or long-term depression (LTD). If we understand how LTP and LTD occur, we will have made great strides towards understanding how learning and memory take place. 4) Deduce a means to include synaptic modification in models that is consistent with experimental observations of LTP and LTD. This research will provide a quantitative understanding of computation and synaptic modification in dentate granule cells. This will tell us how highly detailed models might be reduced to simple descriptions of dentate granule cells that retain the essential computational features of these cells. These simple descriptions can then be used in complex network models to investigate hippocampal function.

这项研究的长期目标是了解 海马。海马被认为在 学习和记忆功能，并参与了许多专业 神经系统疾病。如果我们要了解海马功能，我们 必须了解计算和突触修改的方式 海马细胞。 计算机建模是研究海马的新工具 功能。他可以用来测试单个神经元的计算机模型 假设难以通过实验解决，并且可以提供特定的 关于观察到现象机制的预测。在这项研究中 海马齿状颗粒细胞的高度详细模型将是 发达。这些模型将包括完整的形态以及 突触和非突触电导的数学描述以及 控制细胞中钙浓度的过程。模型将是 使与相当大的身体保持一致 可用的实验数据。 这些高度详细的模型将用于：1）评估的重要性 齿状功能的形态和电子结构 颗粒细胞。 2）确定计算可能性的范围 这些单元格给了它们对离子通道类型，分布和 密度。确定时计算的可能性如何改变 参数值变化可能会揭示某些现象 病理状况。 3）解释钙浓度如何变化 该单元可能与诱导长期增强有关 （LTP）或长期抑郁（LTD）。如果我们了解LTP和LTD 发生，我们将在了解学习方式方面取得了长足的进步 和内存发生。 4）推断出一种包括突触修改的方法 在与LTP和LTP实验性观察一致的模型中 有限公司 这项研究将对计算和 齿状颗粒细胞中的突触修饰。这会告诉我们如何 高度详细的模型可能会简化为齿状的简单描述 保留这些基本计算特征的颗粒细胞 细胞。这些简单的描述然后可以在复杂的网络中使用 研究海马功能的模型。