Modeling microcircuits of realistic hippocampal neurons

模拟真实海马神经元的微电路

• 批准号: 7588736
• 负责人: NELSON P. SPRUSTON
• 金额: $ 31.97万
• 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 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7588736
• 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; Hand; Hippocampus (Brain); Internet; Interneurons; Investigation; Joints; Knowledge; Label; Learning; Measures; Mediating; Membrane; Memory; Methods; Modeling; Morphology; Mus; Neural Network Simulation; Neurons; Philosophy; Physics; Physiological; Population; Population Heterogeneity; Population Study; 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)：神经元回路在许多水平上表现出专门化；特别是神经元多样性和连接上的差异被认为是至关重要的。在理解可能有助于海马体学习和记忆的可塑性类型方面取得了重大进展，但关于该回路如何存储和提取信息的研究要少得多。所有回路功能的一个关键方面是抑制性中间神经元的不同群体，它们在生理特性、树突形态和轴突靶向方面存在差异。通过在系统的详细计算机模型中捕获神经元多样性和连接性所固有的复杂性，可以显著提高对电路功能的理解。在这里，我们建议对NINDS-Gensat项目产生的BAG转基因小鼠的海马区中间神经元上的特定种群进行研究和建模。我们建议记录这些小鼠中已识别的神经元，以确定它们的生理特性。记录的细胞也将被染色，以便树突的形态可以被确定和量化。然后，将生成它们投射到的中间神经元和锥体神经元的计算模型，目的是对海马体电路功能进行可实验检验的预测。这是一个合作项目，将研究人员、学生和博士后聚集在一起，采取多学科的方法来研究海马体电路功能。该项目有五个具体目标：1)BAG转基因小鼠海马区中间神经元的生理研究。2)BAG转基因小鼠海马神经元的解剖学研究。3)BAG转基因小鼠中间神经元调控的研究。4)用BAG转基因小鼠建立海马神经元模型。5)开发用于微电路建模的先进计算方法。这项拟议的工作对包括阿尔茨海默病、癫痫和精神分裂症在内的几种神经疾病具有重要意义。