Abstract. Simulations have become key in many scientific disciplines to better understand natural phenomena. Neuroscientists, for example, build and simulate increasingly fine-grained models (including subcellular details, e.g., neurotransmitter) of the neocortex to understand the mechanisms causing brain diseases and to test new treatments in-silico. The sheer size and, more importantly, the level of detail of their models challenges today's spatial data management techniques. In collaboration with the Blue Brain project (BBP) we develop new approaches that efficiently enable analysis, navigation and discovery in spatial models of the brain. More precisely, we develop an index for the scalable and efficient execution of spatial range queries supporting model building and analysis. Furthermore, we enable navigational access to the brain models, i.e., the execution of of series of range queries where he location of each query depends on the previous ones. To efficiently support navigational access, we develop a method that uses previous query results to prefetch spatial data with high accuracy and therefore speeds up navigation. Finally, to enable discovery based on the range queries, we conceive a novel in-memory spatial join. The methods we develop considerably outperform the state of the art, but more importantly, they enable the neuroscientists to scale to building, simulating and analyzing massively bigger and more detailed brain models.