Modeling microcircuits of realistic hippocampal neurons

模拟真实海马神经元的微电路

基本信息

批准号：
8134703
负责人：
NELSON P. SPRUSTON
金额：
$ 7.63万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
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/8134703
关键词：
Affect Alzheimer&apos 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

项目摘要

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）：神经元回路在许多层面上表现出专业化；特别是，神经元的多样性和连接性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已经取得了重大进展，但对于该电路如何存储和提取信息的了解却少之又少。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，它们在生理特性、树突形态和轴突靶向方面有所不同。通过捕捉系统详细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，我们建议对 NINDS-Gensat 项目产生的 BAG 转基因小鼠中鉴定的海马中间神经元上的特定群体进行研究和建模。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，以便可以确定和量化树突形态。然后将生成中间神经元和锥体神经元的计算模型，它们将投影到这些模型上，以便对海马回路功能进行可实验测试的预测。这是一个合作项目，汇集了研究人员、学生和博士后，采用多学科方法来研究海马回路功能。该项目有五个具体目标：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调节的研究。 4) 对 BAG 转基因小鼠的海马中间神经元进行建模。 5）开发微电路建模的先进计算方法。这项拟议的工作对多种神经系统疾病具有重要意义，包括阿尔茨海默病、癫痫和精神分裂症。