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业化;特别是，神经元多样性和连接差异被认为是至关重要的。在理解海马体中可能有助于学习和记忆的可塑性类型方面已经取得了重大进展，但关于回路如何存储和提取信息的发现要少得多。所有回路功能的一个关键方面是抑制性中间神经元的多样性群体，其在生理特性、树突形态和轴突靶向方面不同。电路功能的理解，可以显着提高通过捕获的复杂性内在的神经元的多样性和连接的详细的计算机模型的系统。在这里，我们提出了研究和模型的特定群体的中间神经元在海马中确定的BAG转基因小鼠产生的NINDS-Gensat项目。我们建议从这些小鼠中识别出的神经元中记录，以确定它们的生理特性。还将对记录的细胞进行染色，以便可以确定和定量树突状形态。然后将生成中间神经元和锥体神经元的计算模型，它们投射到这些中间神经元和锥体神经元上，目的是对海马电路功能进行实验可检验的预测。这是一个合作项目，汇集了研究人员、学生和博士后，采用多学科方法研究海马回路功能。本研究的具体目标有五个：1）BAG转基因小鼠海马中间神经元的生理学研究。2)BAG转基因小鼠海马中间神经元的解剖学研究。3)BAG转基因小鼠中间神经元的调制研究。4)从BAG转基因小鼠建模海马中间神经元。5)发展先进的微电路建模计算方法。这项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系统疾病具有重要意义。