Project Abstract The project "Evolutionary Pathways of Memory: Multiomic Analysis of the Entorhinal Cortex across Mammals" focuses on the entorhinal cortex (EC), a pivotal region for episodic memory and spatial navigation that is essential for survival and adaptive behavior across species. The EC integrates information from the neocortex, which is then relayed to the hippocampus, playing a crucial role in the consolidation and retrieval of memories. Its evolutionary significance and vulnerability to neurodegenerative diseases, particularly Alzheimer's, make it a focal point for understanding the evolution of cognitive functions and disease mechanisms. This proposal aims to systematically compare the EC across 14 mammalian species, using state-of-the-art single-cell genomics and spatial transcriptomics to elucidate the cellular composition, gene expression patterns, and regulatory landscapes that have evolved over approximately 180 million years. The research plan is structured to dissect the evolutionary conservation and divergence of cell types within the EC, identify species-specific adaptations, and uncover the molecular underpinnings of these processes. By integrating single-nucleus RNA sequencing, ATAC sequencing for chromatin accessibility, and spatially resolved transcriptomics, the project will generate comprehensive cell type atlases that highlight evolutionary trends in neuronal and non-neuronal cells. This multi-layered analysis will help identify conserved genetic circuits critical for memory and navigation, and human-specific alterations that may be relevant to neurological diseases. A significant component of this proposal is the dedicated mentorship and training plan for Jessie Puckett. As an emerging scientist, Jessie will be immersed in a multidisciplinary training program that includes hands-on experience in advanced genomic technologies, computational data analysis, and evolutionary biology. Mentorship will be provided by leading experts in genomics, neuroscience, and bioinformatics, ensuring a broad and deep educational experience. Regular progress meetings, workshops on scientific communication, and opportunities to present findings at conferences will further enhance Jessie's professional development. This mentorship strategy is designed not only to advance the project's aims but also to equip Jessie with a diverse analytical skill set and biological background, positioning her for a successful career in the biomedical sciences. This project brings together evolutionary biology, genomics, and computational analysis to explore key aspects of brain cellular architecture. Through its ambitious research objectives and comprehensive training program, it aims to generate novel insights into the evolutionary adaptations of the entorhinal cortex, while fostering the growth of an adept and innovative scientist.