Modeling microcircuits of realistic hippocampal neurons

模拟真实海马神经元的微电路

• 批准号: 8051710
• 负责人: William Lawrence Kath
• 金额: $ 31.23万
• 依托单位: NORTHWESTERN UNIVERSITY
• 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 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8051710
• 关键词: Affect; Alzheimer' s Disease; Award; Axon; Bacterial Artificial Chromosomes; Biological; Biological Models; Biological Sciences; Cells; Collaborations; Computer Simulation; Computing Methodologies; Corpus striatum structure; Data; Dendrites; Dopamine; Dopamine D2 Receptor; Engineering; Environment; Epilepsy; Exhibits; Goals; Grant; Hippocampus (Brain); Internet; Interneurons; Investigation; Joints; Knowledge; Label; Learning; Mathematics; Measures; Mediating; Membrane; Memory; Methods; Modeling; Morphology; Mus; National Institute of Neurological Disorders and Stroke; Neural Network Simulation; Neurobiology; Neurons; Philosophy; Physics; Physiological; Population; Population Heterogeneity; Population Study; Postdoctoral Fellow; Prefrontal Cortex; Process; Progress Reports; Property; Research; Research Personnel; Research Training; Resources; Running; Schizophrenia; Serotonin; Speed; Staining method; Stains; Students; Study models; Sum; Synapses; Synaptic Transmission; System; Testing; Training; Transgenic Mice; Trees; United States National Institutes of Health; Universities; Work; alveus; cell type; computational neuroscience; hippocampal pyramidal neuron; improved; insight; interdisciplinary approach; interdisciplinary collaboration; medical schools; models and simulation; nervous system disorder; neural circuit; parallel architecture; patch clamp; programs; receptor; research study; simulation; synaptic function; tool

DESCRIPTION (provided by applicant): Neuronal circuits exhibit specialization at many levels; in particular, neuronal diversity and differences in connectivity are thought to be crucial. Significant advances have been made in understanding the types of plasticity that may contribute to learning and memory in the hippocampus, but much less has been discovered about how the circuit stores and extracts information. A key aspect of all circuit function is the diverse population of inhibitory interneurons, which differ in physiological properties, dendritic morphology and axon targeting. Understanding of circuit function can be significantly enhanced by capturing the complexity inherent in neuronal diversity and connectivity in detailed computer models of the system. Here we propose to study and model specific populations on interneurons in the hippocampus identified in BAG transgenic mice generated by the NINDS-Gensat project. We propose to record from identified neurons in these mice in order to determine their physiological properties. The recorded cells will also be stained so that dendritic morphology can be determined and quantified. Computational models will then be generated of the interneurons and pyramidal neurons to which they project for the purpose of making experimentally testable predictions concerning hippocampal circuit function. This is a collaborative project that brings together investigators, students, and postdocs to take a multidisciplinary approach to the study of hippocampal circuit function. The project has five specific aims: 1) Physiological investigation of hippocampal interneurons in BAG transgenic mice. 2) Anatomical investigation of hippocampal interneurons in BAG transgenic mice. 3) Studies of modulation of interneurons in BAG transgenic mice. 4) Modeling hippocampal interneurons from BAG transgenic mice. 5) Developing advanced computational methods for microcircuit modeling. The proposed work has important implications for several neurological disorders, including Alzheimer's disease, epilepsy, and schizophrenia.

描述（由申请人提供）：神经元电路在许多层面上表现出专业化；特别是，神经元的多样性和连通性的差异被认为至关重要。在理解可能导致海马学习和记忆的可塑性类型方面取得了重大进展，但是关于电路存储和提取信息的信息少得多。所有电路函数的一个关键方面是抑制性中间神经元的多样化，它们在生理特性，树突形态和轴突靶向方面有所不同。通过捕获系统详细的计算机模型中神经元多样性和连接性固有的复杂性，可以显着增强对电路功能的理解。在这里，我们建议在Ninds-Gensat项目产生的袋子转基因小鼠中鉴定出的海马中的中间神经元和对特定人群进行研究。我们建议从这些小鼠中识别的神经元记录下来，以确定其生理特性。记录的细胞也将被染色，以便可以确定和定量树突形态。然后，将生成其投射到的中间神经元和锥体神经元的中间神经元和锥体神经元，以便对海马电路功能进行实验测试的预测。这是一个协作项目，将研究人员，学生和博士后汇集在一起​​，以多学科的方法来研究海马巡回赛功能。该项目具有五个特定的目的：1）袋转基因小鼠中海马中间神经元的生理研究。 2）袋转基因小鼠中海马中间神经元的解剖学研究。 3）研究袋转基因小鼠中神经元调节的研究。 4）对袋子转基因小鼠的海马中间神经元进行建模。 5）开发用于微电路建模的高级计算方法。拟议的工作对包括阿尔茨海默氏病，癫痫和精神分裂症在内的几种神经系统疾病具有重要意义。

项目成果

Coincidence detection of place and temporal context in a network model of spiking hippocampal neurons.

• DOI: 10.1371/journal.pcbi.0030234
• 发表时间: 2007-12
• 期刊: PLoS computational biology
• 影响因子: 4.3
• 作者: Katz Y;Kath WL;Spruston N;Hasselmo ME
• 通讯作者: Hasselmo ME

Slow integration leads to persistent action potential firing in distal axons of coupled interneurons.

• DOI: 10.1038/nn.2728
• 发表时间: 2011-02
• 期刊: NATURE NEUROSCIENCE
• 影响因子: 25
• 作者: Sheffield, Mark E. J.;Best, Tyler K.;Mensh, Brett D.;Kath, William L.;Spruston, Nelson
• 通讯作者: Spruston, Nelson

Computational modeling of dendrites.

树突的计算模型。

• DOI: 10.1002/neu.20154
• 发表时间: 2005
• 期刊: Journal of neurobiology.
• 作者: Kath,WilliamL