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一个关于啮齿动物海马结构中突触电生理学的综合知识库。

A comprehensive knowledge base of synaptic electrophysiology in the rodent hippocampal formation.

机构信息

Neuroscience Program, Krasnow Institute for Advanced Study, George Mason University, Fairfax, Virginia.

Bioengineering Department, Krasnow Institute for Advanced Study, George Mason University, Fairfax, Virginia.

出版信息

Hippocampus. 2020 Apr;30(4):314-331. doi: 10.1002/hipo.23148. Epub 2019 Aug 31.

Abstract

The cellular and synaptic architecture of the rodent hippocampus has been described in thousands of peer-reviewed publications. However, no human- or machine-readable public catalog of synaptic electrophysiology data exists for this or any other neural system. Harnessing state-of-the-art information technology, we have developed a cloud-based toolset for identifying empirical evidence from the scientific literature pertaining to synaptic electrophysiology, for extracting the experimental data of interest, and for linking each entry to relevant text or figure excerpts. Mining more than 1,200 published journal articles, we have identified eight different signal modalities quantified by 90 different methods to measure synaptic amplitude, kinetics, and plasticity in hippocampal neurons. We have designed a data structure that both reflects the differences and maintains the existing relations among experimental modalities. Moreover, we mapped every annotated experiment to identified potential connections, that is, specific pairs of presynaptic and postsynaptic neuron types. To this aim, we leveraged Hippocampome.org, an open-access knowledge base of morphologically, electrophysiologically, and molecularly characterized neuron types in the rodent hippocampal formation. Specifically, we have implemented a computational pipeline to systematically translate neuron type properties into formal queries in order to find all compatible potential connections. With this system, we have collected nearly 40,000 synaptic data entities covering 88% of the 3,120 potential connections in Hippocampome.org. Correcting membrane potentials with respect to liquid junction potentials significantly reduced the difference between theoretical and experimental reversal potentials, thereby enabling the accurate conversion of all synaptic amplitudes to conductance. This data set allows for large-scale hypothesis testing of the general rules governing synaptic signals. To illustrate these applications, we confirmed several expected correlations between synaptic measurements and their covariates while suggesting previously unreported ones. We release all data open-source at Hippocampome.org in order to further research across disciplines.

摘要

啮齿动物海马体的细胞和突触结构已在数千篇经过同行评审的出版物中进行了描述。然而,对于这个或任何其他神经系统,都没有可供人类或机器读取的突触电生理学公共目录。我们利用最先进的信息技术,开发了一个基于云的工具集,用于从科学文献中识别与突触电生理学相关的实证证据,提取相关的实验数据,并将每个条目链接到相关的文本或图形摘录。挖掘了超过 1200 篇已发表的期刊文章,我们确定了 8 种不同的信号模式,通过 90 种不同的方法来量化海马神经元的突触幅度、动力学和可塑性。我们设计了一种数据结构,既能反映实验模式之间的差异,又能保持其现有关系。此外,我们将每个注释的实验映射到已识别的潜在连接,即特定的突触前和突触后神经元类型的特定对。为此,我们利用 Hippocampome.org,这是一个开放获取的知识基础,其中包含了啮齿动物海马体结构中形态学、电生理学和分子学特征的神经元类型。具体来说,我们实现了一个计算管道,系统地将神经元类型的属性转化为正式查询,以便找到所有兼容的潜在连接。通过这个系统,我们收集了近 40000 个突触数据实体,涵盖了 Hippocampome.org 中 3120 个潜在连接的 88%。根据液体结电位校正膜电位,显著降低了理论和实验反转电位之间的差异,从而能够将所有突触幅度准确转换为电导。这个数据集允许对支配突触信号的一般规则进行大规模的假设检验。为了说明这些应用,我们验证了一些预期的相关性,即突触测量及其协变量之间的相关性,同时还提出了一些以前未报告的相关性。我们将所有数据在 Hippocampome.org 上开源,以便在跨学科领域进一步研究。

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