Glioblastoma (GBM) is a frequent, treatment resistant adult brain tumour which is classified as a grade IV glioma (Louis et al., 2016). To date treatment options for glioblastoma brain tumours are limited and no reliable markers are available to distinguish migratory active from resting glioblastoma cells. Here, we investigated the rat glioblastoma cell line C6 and their invasive behaviour on living brain tissue, represented by rat hippocampal slice cultures. We established a model system where brain tissue (represented by organotypic slice cultures) is overlayed with fluorescently labelled glioblastoma cells. Our aim is to explore local interactions of glioblastoma C6 cells with neural tissue with focus on interactions that promote glioblastoma cell migratory behaviour. In the long term, we want to use our model system to explore the behaviour of human GBM cells in rodent brain tissue environment, similar as recently reported (Mann et al., 2023). In our model system we can observe the single cell migration mode and infiltrative tumour growth of GBM, cell behaviours that are characteristic for GBM. For instance, effects of the extracellular matrix protein reelin on C6 glioma cell behaviour were described. We are therefore interested in the response of GBM cells to reelin enriched cell layers, such as the outer molecular layer of the dentate gyrus in hippocampal organotypic slice cultures (Förster et al. 2006). We expect to acquire new insights into local interactions of glioblastoma cells with their local tissue environment.