Structural mapping of neural systems in developing and adult rodents
Diseases afflicting the brain during development and ageing cause cognitive, motor, and emotional dysfunction. To better diagnose, understand, and amend such disorders, we first need better knowledge about the normal neural architecture. This project aims to map and quantify structural features of neural networks in young, adult and aging rats and mice. We will use combinations of (immuno)-histochemistry and axonal tracing techniques to label a range of cellular, subcellular components and neural connections in rodent brains at different ages. Labelled features will be visualized using high-resolution slide scanning and two-photon microscopy, and microscopic images will be analyzed using digital atlasing tools and computational image analyses. The microscopic images, describing regional and subregional spatial distribution of specific cellular markers and axonal connections in the cerebral cortex and subcortical structures, will be organized in a neuroinformatics database system developed in our laboratory, and publicly shared via the EBRAINS Knowledge Graph (https://search.kg.ebrains.eu/?facet_type[0]=Dataset). Images will be co-registered to three-dimensional digital reference atlases for the rat and mouse brain to facilitate efficient analyses, comparison and integration of data. The project is associated with the EU Future Emerging Technologies Flagship project “The Human Brain Project”, to which we contribute with development of rodent brain atlases and pipelines for analysis and sharing of large amounts of neuroscience data.
Most animals will only be terminally anaesthetized and sacrificed for tissue extraction. Some animals will receive intracranial injections of very small volumes of axonal tracers. Aging animals and animals undergoing experimental perturbations will be regularly monitored by researchers and animal housing staff, who will assess and score animals appearance, behaviour, weight and movement. Significant changes in health score (according to predefined criteria) or > 15 % weight loss will be considered as a humane endpoint where animals will be sacrificed. We will use 70 mice and 70 rats to create a comprehensive collection of data showing the development of structural features if the brain. These are data that are of interest for a broad range of purposes in the field of neuroscience. The systematic mapping and sharing of data as planned here can potentially reduce the need for using new animals in the future, as other researchers will be able to access and re-use our material.
Most animals will only be terminally anaesthetized and sacrificed for tissue extraction. Some animals will receive intracranial injections of very small volumes of axonal tracers. Aging animals and animals undergoing experimental perturbations will be regularly monitored by researchers and animal housing staff, who will assess and score animals appearance, behaviour, weight and movement. Significant changes in health score (according to predefined criteria) or > 15 % weight loss will be considered as a humane endpoint where animals will be sacrificed. We will use 70 mice and 70 rats to create a comprehensive collection of data showing the development of structural features if the brain. These are data that are of interest for a broad range of purposes in the field of neuroscience. The systematic mapping and sharing of data as planned here can potentially reduce the need for using new animals in the future, as other researchers will be able to access and re-use our material.