General principles of structural maturation and integration of newly born granule cells in the hippocampal network studied by time-lapse imaging and computational models

成年神经发生在海马区发挥着独特的作用，因为它导致新生神经元整合到一个具有明确连接的预先形成的回路中，并与新记忆的形成直接相关。在这里，我们将利用出生后和成年出生的齿状颗粒细胞(GC)的成熟来研究新神经元整合到现有网络中的算法实现，以及这一过程在树突形成的时间动力学中的反映方式。我们将树突状棘突的发生与功能整合的关键时间段联系起来。我们的建议侧重于以下问题：结构性增长过程的动力是什么？脊柱形成和功能整合是否导致树突状结构的稳定？什么动态过程决定了成熟海马区的树突树结构？为了解决这些问题，我们将使用最先进的实验程序，将详细的体外时间推移分析与体内数据的大型数据库以及精确的生物物理和形态建模技术相结合。这一结果将使我们能够剖析树突状细胞成熟的计算作用以及成年出生GC整合在海马网络中的动力学。我们将采用实验和建模相结合的方法，研究网络活动对新生神经元树突修剪的影响。最近发展的基于最优连接原则的新的形态建模方法将使我们能够确定齿状颗粒细胞生长和网络整合的一般原理。树突和棘突的3D重建、它们的形态测量以及新生的齿状颗粒细胞的新的和大大改进的、解剖学上逼真的形态模型将免费提供给科学界。

Adult neurogenesis plays a unique role in the hippocampus because it leads to the integration of newborn neurons into a preformed circuit with well-defined connectivity and is directly linked with the formation of novel memories. Here, we will take advantage of the maturation of postnatally and adult-born dentate granule cells (GCs) to study the algorithmic implementation of the integration process of new neurons into existing networks and the way in which this is reflected in the temporal dynamics of dendritic tree formation. We will link dendritic spinogenesis with the critical time period of functional integration. Our proposal focuses on following questions: What are the dynamics of the structural growth process? Do spine formation and functional integration lead to stabilization of dendritic structures? What dynamic processes determine dendritic tree structure in the mature hippocampus? To address these issues we will use state-of-the-art experimental procedures combining detailed in vitro time-lapse analyses with a large database of in vivo data and precise biophysical and morphological modelling techniques. The results will allow us to dissect the computational role of dendritic tree maturation as well as the dynamics of adult born GC integration in the hippocampal network. Using combined experimental and modeling approach, we will study the effects of network activity on the pruning of dendritic branches in newborn neurons. Recently developed new methods of morphological modeling based on optimal wiring principles will enable us to identify general principles of growth and network integration of dentate granule cells. 3D-reconstructions of dendrites and spines, their morphological measurements as well as new and greatly improved, anatomically realistic morphological models of newly-born dentate granule cells will be freely available for the scientific community.