Blue Brain Project, École polytechnique fédérale de Lausanne (EPFL), Campus Biotech, Geneva, Switzerland.
HUN-REN Institute of Experimental Medicine (KOKI), Budapest, Hungary.
PLoS Biol. 2024 Nov 5;22(11):e3002861. doi: 10.1371/journal.pbio.3002861. eCollection 2024 Nov.
The CA1 region of the hippocampus is one of the most studied regions of the rodent brain, thought to play an important role in cognitive functions such as memory and spatial navigation. Despite a wealth of experimental data on its structure and function, it has been challenging to integrate information obtained from diverse experimental approaches. To address this challenge, we present a community-based, full-scale in silico model of the rat CA1 that integrates a broad range of experimental data, from synapse to network, including the reconstruction of its principal afferents, the Schaffer collaterals, and a model of the effects that acetylcholine has on the system. We tested and validated each model component and the final network model, and made input data, assumptions, and strategies explicit and transparent. The unique flexibility of the model allows scientists to potentially address a range of scientific questions. In this article, we describe the methods used to set up simulations to reproduce in vitro and in vivo experiments. Among several applications in the article, we focus on theta rhythm, a prominent hippocampal oscillation associated with various behavioral correlates and use our computer model to reproduce experimental findings. Finally, we make data, code, and model available through the hippocampushub.eu portal, which also provides an extensive set of analyses of the model and a user-friendly interface to facilitate adoption and usage. This community-based model represents a valuable tool for integrating diverse experimental data and provides a foundation for further research into the complex workings of the hippocampal CA1 region.
海马体的 CA1 区域是啮齿动物大脑中研究最多的区域之一，被认为在记忆和空间导航等认知功能中发挥重要作用。尽管有大量关于其结构和功能的实验数据，但整合来自不同实验方法的信息一直具有挑战性。为了解决这一挑战，我们提出了一个基于社区的、全面的大鼠 CA1 计算机模型，该模型整合了广泛的实验数据，从突触到网络，包括其主要传入神经——沙费尔侧支的重建，以及乙酰胆碱对系统影响的模型。我们测试和验证了每个模型组件和最终的网络模型，并使输入数据、假设和策略变得明确和透明。该模型的独特灵活性允许科学家们潜在地解决一系列科学问题。在本文中，我们描述了用于设置模拟以重现体外和体内实验的方法。在本文的几个应用中，我们重点介绍了 theta 节律，这是一种与各种行为相关性相关的突出的海马体振荡，我们使用我们的计算机模型来重现实验结果。最后，我们通过 hippocampushub.eu 门户提供数据、代码和模型，该门户还提供了对模型的广泛分析以及用户友好的界面，以促进采用和使用。这个基于社区的模型代表了整合不同实验数据的有价值的工具，并为进一步研究海马体 CA1 区域的复杂工作原理提供了基础。
