Many psychiatric and neurological diseases are characterized by a decrease in grey matter volume (GMV). Conversely, enhanced neuronal activity due to learning may cause an increase in GMV. Our knowledge about the underlying biological mechanisms is still in its infancy. The present project is combining cutting edge in vivo (MRI) and ex vivo (Ultramicroscopy) imaging approaches in double or triple genetically modified mice to demonstrate a direct link between increased neuronal activity during spatial learning, GMV changes and alterations in dendritic morphology. In this context we will apply whole-brain voxel-wise analyses to obtain a circumscribed pattern of hot spots in neuronal activity and GMV alterations during different phases of spatial learning and memory, thus broadening the hippocampus-centric concepts of spatial navigation. We will use pharmacogenetic inhibition or activation of neuronal populations "tagged" during spatial learning (i) to demonstrate their causal involvement in memory processes, (ii) to interfere with their activity during memory consolidation, (iii) to enhance/ impair long-term retention of spatial memory and (iv) relate the memory changes to alterations in GMV and dendritic morphology. The last point becomes feasible by recent improvements in our Ultramicroscopy imaging technique. This project will combine in vivo and ex vivo whole brain analyses at 4 orders of magnitude providing insights in changes in the brain during learning.