Integration of gene expression and brain-wide connectivity reveals the multiscale organization of mouse hippocampal networks

Understanding the organization of the hippocampus is fundamental to understanding brain function related to learning, memory, emotions, and diseases like Alzheimer’s disease. Physiological studies in humans and rodents suggest both structural and functional heterogeneity along the longitudinal axis of the hippocampus. Yet the recent discovery of discrete gene expression domains within the mouse hippocampus has provided the opportunity to re-evaluate hippocampal connectivity. To integrate mouse hippocampal gene expression and connectivity, we mapped the distribution of distinct gene expression patterns within mouse hippocampus and subiculum to create the Hippocampus Gene Expression Atlas (HGEA). Notably, novel subiculum gene expression patterns revealed a hidden laminar organization. Guided by the HGEA, we constructed the most detailed hippocampal connectome available using Mouse Connectome Project (www.MouseConnectome.org) tract tracing data. Our results define the hippocampus’ multiscale network organization and demonstrate each subnetwork’s unique brain-wide connectivity patterns.