SenseLab: Integration of Multidisciplinary Sensory Data

描述（由申请人提供）：SenseLab套件包含8个可互操作的数据库，旨在支持我们对大脑组织，嗅球模型系统的研究，并与神经科学和神经信息学社区共享这些和相关资源。在过去的5年里，一项计划项目资助使我们能够开始从突触和细胞水平转移到微电路水平，在这项R01资助中，我们将直接建立在这项工作的基础上。首先，我们将继续开发使用最频繁的数据库——NeuronDB和ModelDB——用于分析树突信号整合，以及ORDB，支持研究嗅觉受体（基因组中最大的家族）。我们将继续参与神经科学数据库门户、神经科学信息框架和国际神经信息学协调设施。我们将继续通过两个新的研究项目来展示数据库如何支持神经科学研究，以开发能够深入了解实验数据的计算模型。其中一个项目是深入了解我们最近从跨突触追踪广泛分布的细胞柱的实验证据，我们假设这些细胞柱参与处理气味地图。我们将分析这些数据，并利用它来完善一个简化的微电路，在这个微电路中，肾小球细胞柱对来自气味图的兴奋性输入作出反应，并通过肾小球柱之间的距离无关的侧抑制来处理它。通过实验数据的持续测试，我们将把模型扩展到100列，然后扩展到2000列，以表征气味地图的全局处理，达到实验方法无法达到的程度。这项工作将作为一个试点项目，与瑞士的蓝脑项目并行进行，以现实为基础的大规模皮层网络。将开发一个新的数据库MicrocircuitDB，以支持这一研究和微电路组织的相关研究。第二个新项目将把我们对嗅觉肾小球能量需求的计算分析扩展到侧抑制相互作用，以提供对处理气味地图的微电路能量需求的更彻底的理解。一个新的数据库项目是应用NeuronDB和ModelDB分析神经退行性疾病早期发病机制对树突信号整合的影响。为此，我们正在开发一个新的数据库，脑药理学（BrainPharm）。所有这些工作都将受益于耶鲁医学信息学中心和神经元模拟环境团队的持续支持和发展。公共卫生相关性：迫切需要了解信号是如何在神经细胞和神经回路中处理的，这是脑功能的基础。我们试图通过一个相互关联的实验数据和计算机模型数据库系统来加强这一努力。这些新项目将使人们对正常的大脑功能和阿尔茨海默病等神经系统疾病有更深入的了解

DESCRIPTION (provided by applicant): The SenseLab suite of 8 interoperable databases is aimed at supporting our research on a model system for brain organization, the olfactory bulb, and at sharing these and related resources with the neuroscience and neuroinformatics communities. During the past 5 years a Program Project grant has enabled us to begin to move from the synaptic and cell levels to the microcircuit level, and in this R01 grant we will build directly on this work. First, we will continue development of our most heavily used databases - NeuronDB and ModelDB - for the analysis of dendritic signal integration, and ORDB, supporting work on olfactory receptors, the largest family in the genome. We will continue to participate in the Neuroscience Database Gateway, the Neuroscience Information Framework, and the International Neuroinformatics Coordinating Facility. We will continue to demonstrate how databases support neuroscience research with two new research projects to develop computational models that give insight into experimental data. One project is to deepen insight into our recent experimental evidence from transsynaptic tracing for widely distributed cell columns, which we hypothesize are involved in processing odor maps. We will analyze this data and use it to refine first a reduced microcircuit in which the glomerular cell columns respond to the excitatory input from the odor maps and process it through distance-independent lateral inhibition between glomerular columns. With continual testing by the experimental data, we will scale up the model to 100 columns, then to 2,000, to characterize the global processing of odor maps to an extent not possible with experimental methods. This work will be carried out as a pilot project in parallel with the Blue Brain Project in Switzerland on realistically-based large- scale cortical networks. A new database, MicrocircuitDB, will be developed to support this and related studies of microcircuit organization. A second new project will extend our computational analysis of energy demands in the olfactory glomerulus to the lateral inhibitory interactions, to provide a more thorough understanding of the energy demands of the microcircuits that process odor maps. A new database project is to apply NeuronDB and ModelDB to analyzing the impact of the early pathogenesis of neurodegenerative disorders on dendritic signal integration. For this purpose we are developing a new database, Brain Pharmacology (BrainPharm). All of this work will benefit from continued support and development by the Yale Center for Medical Informatics, and by the NEURON simulation environment team. PUBLIC HEALTH RELEVANCE: There is a critical need to understand how signals are processed in nerve cells and nerve circuits as a basis for brain function. We attempt to enhance this effort through a system of interrelated databases of experimental data and computer models. The new projects should give a deeper understanding of both normal brain function and neurological disorders such as Alzheimer's disease