Resolving cellular and molecular diversity along the hippocampal anterior-to-posterior axis in humans

The hippocampus supports many facets of cognition, including learning, memory, and emotional processing. Anatomically, the hippocampus runs along a longitudinal axis, posterior to anterior in primates. The structure, function, and connectivity of the hippocampus vary along this axis. In human hippocampus, longitudinal functional heterogeneity remains an active area of investigation, and structural heterogeneity has not been described. To understand the cellular and molecular diversity along the hippocampal long axis in human brain and define molecular signatures corresponding to functional domains, we performed single-nuclei RNA sequencing on surgically resected human anterior and posterior hippocampus from epilepsy patients, identifying differentially expressed genes at cellular resolution. We further identify axis-and cell-type -specific gene expression signatures that differentially intersect with human genetic signals, identifying cell type-specific genes in the posterior hippocampus for cognitive function and the anterior hippocampus for mood and affect. These data are accessible as a public resource through an interactive website.

Automated summary

The hippocampus plays a crucial role in cognition, with functional and structural variances along its longitudinal axis in humans. Single-nuclei RNA sequencing on surgically resected human hippocampus revealed differentially expressed genes, identifying specific functions of different cell types within the hippocampus.