Generation and Description of Neuronal Morphology and Connectivity

树突状和轴突形态在生理、脑功能和病理中起着基础性作用 通过影响突触整合、棘波传递和电路连接而导致的功能障碍。合并 发表的实验数据是准确的、全面的和生物学上可信的神经网络模拟 这对于在亚细胞和系统层面上建立定量的桥梁非常重要。我们成功地设计了， 实施并免费分发给社区计算机软件和数据库以重建， 分析、可视化、模拟和共享从任何标记和 可视化技术、动物种类、大脑区域、发育阶段和实验条件。 我们用光学显微镜成像，数字追踪，并分享新的数据，我们为同行提供了 电子手段可以自由地做同样的事情。此外，我们将这些数据与计算模型相结合 膜生物物理学研究神经元结构-活性关系，特别关注 海马体和内嗅皮层由于其在空间表征和情景记忆中的中心作用。我们 此外，还在开源的基于Web的神经元门户中注释了大量的细胞属性 啮齿动物海马区的类型。我们现在建议将这一研究方法扩展为三个 明确的目标。第一个是增强NeuroMorphy的功能、范围和可用性。 数字痕迹。我们计划将共享重建的数量增加一倍以上，同时增强 人和机器可访问的实用程序，增加了“相似搜索”和摘要报告功能。多数 对于长远的可持续发展，我们将大力推进信息技术基础设施的现代化 支持直接来自作者的未经请求的提交、持续的敏捷发布以及 社区众包。第二个目标是通过添加以下内容来完善Hippocampome.org知识库 突触信息，包括连接概率、生理和可塑性，并将它们与 突触前和突触后神经元的现有形态、生理和分子特性。这将是 能够实施真实规模的尖峰神经网络模型来运行活动的预测性模拟 动力学和计算功能。第三个目标是开发一种创新的方法来对神经元进行分类 直接从网络连接，使用海马体电路进行验证，并将其部署在开放访问上 来自一种流行的生物模型的高通量数据。这三个目标加在一起，将使我们(和其他人)能够 一方面，测试将神经元形态与分子和发育决定因素联系起来的假设， 另一端连接到功能电路。这种应用的重点是结构塑性，这一点尤其相关。 使显著累及海马体结构的神经系统疾病致残，包括癫痫和 我们提出的数据驱动的、生物逼真的网络模拟可能有助于阐明 具体的神经元类型及其在记忆形成和提取障碍中的相互作用。

Dendritic and axonal morphologies play fundamental roles in physiological brain function and pathological dysfunction by affecting synaptic integration, spike train transmission, and circuit connectivity. Incorporating published experimental data into accurate, full-scale, and biologically plausible neural network simulations is important for quantitatively bridging the sub-cellular and systems-levels. We successfully designed, implemented, and freely distributed to the community computer software and databases to reconstruct, analyze, visualize, simulate, and share the 3D tree-like shape of neurons collected from any labeling and visualization techniques, animal species, brain regions, developmental stages, and experimental conditions. We imaged by light microscopy, digitally traced, and shared new data, and we provided our peers with the electronic means of freely doing the same. Moreover, we combined those data with computational models of membrane biophysics to investigate the neuronal structure-activity relationship with a special focus on the hippocampus and entorhinal cortex due to their central role in spatial representation and episodic memory. We additionally annotated a massive amount of cellular properties in an open-source web-based portal of neuron types in the rodent hippocampal formation. We now propose to expand this research approach with three specific aims. The first is to augment the power, scope, and usability of the NeuroMorpho.Org repository of digital tracings. We plan to more than double the number of shared reconstructions while enhancing the human- and machine-accessible utility by adding ‘search similar’ and summary reporting functionalities. Most importantly for long-term sustainability, we will dramatically modernize the information technology infrastructure of this resource to enable unsolicited submissions directly from authors, continuous agile releases, and community crowdsourcing. The second aim is to complete the Hippocampome.org knowledge base by adding synaptic information, including connection probabilities, physiology, and plasticity, and linking them to the existing morphological, physiological, and molecular properties of pre- and post-synaptic neurons. This will enable the implementation of a real-scale spiking neural network model to run predictive simulations of activity dynamics and computational functions. The third aim is to develop an innovative approach to classify neurons directly from network connectivity, validating it with the hippocampal circuit and deploying it on open-access high-throughput data from a popular model organism. Together, these three aims will allow us (and others) to test hypotheses relating neuronal morphology to molecular and developmental determinants on the one hand, and to functional circuits on the other. The focus of this application on structural plasticity is especially relevant to disabling neurological diseases prominently involving the hippocampal formation, including epilepsy and Alzheimer’s. Our proposed data-driven, biologically realistic network simulations may shed light on the role of specific neuron types and of their interactions in impairments of memory formation and retrieval.