The entorhinal cortex (EC) plays an important role in memory and navigational processes. The EC is part of the three-layered allocortex and interestingly, the structure in several cortical areas of the reptilian ancestor of mammals was three-layered as well. The EC is shown to be affected in Alzheimer’s disease already at preclinical stages. Furthermore, spatial disorientation is a characteristic cognitive symptom in patients suffering from Alzheimer’s disease. To learn about evolutionary similarities of the EC, we carried out single-nuclei RNA sequencing analysis on salmon telencephalon, fruit bat and baboon EC. We include further published EC snRNA-seq datasets to perform cross-species comparison in order to identify conserved cell types of the EC. Moreover, we will use diffusion tensor imaging (DTI) on postmortem animal brains to elucidate the connectivity of the spatial processing centre to other brain regions. The species in this project were selected to represent the major vertebrate groups and to include species that migrate great distances like salmon. In addition, we chose species that navigate via different sensory cues including visual, chemical and echolocation. We have collected brain tissue from leaf cutter ants, sharks, salmons, iguana, pigeons, fruit bats, hippopotamus and baboons. Our aims are to 1. Uncover conserved cell populations within the spatial processing system from an evolutionary perspective and 2. Understand how differences in navigational sensory input alter connectivity in the regions that process spatial navigation. By identifying core cell types important for processing spatial memory, we may be able to identify important gene orthologues.