Regional and laminar organization of the entorhinal cortex in tree shrews based on cytoarchitecture, chemoarchitecture, and connectivity

The entorhinal cortex (EC) is a pivotal interface that integrates multimodal cortical and subcortical information into the hippocampal formation and distributes hippocampal output to widespread telencephalic targets. It is also one of the earliest and most severely affected regions in Alzheimer's disease (AD). The tree shrew (Tupaia belangeri chinensis) has emerged as a promising model for AD research. However, the uncharted organization of tree shrew EC has limited its application in modeling early stages of AD. In this study, we provide a comprehensive anatomical reference for the tree shrew EC by delineating its boundaries, parcellating its medial and lateral subregions, and mapping its laminar connectivity based on cyto- and chemoarchitecture combined with tracing experiments. We found that the tree shrew EC exhibits an intermediate architecture between rodents and monkeys, mirroring its phylogenetic position and potentially links to the gradual evolution of place codes from rodents to primates. This study provides the first detailed entorhinal atlas of this species, establishing a critical foundation for future neural-tracing and electrophysiological investigations. It enhances the utility of the tree shrew in mechanistic studies of spatial coding, conscious memory, as well as a naturalistic model for incipient AD.