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

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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.