Neurite development varies across the hippocampus and covaries with the cellular composition of hippocampal tissue

The hippocampus is a critical brain structure supporting memory encoding and retrieval, yet the development of its microstructure in humans remains unknown. Understanding this development may provide insight into the mechanisms underlying memory and their disruption in disease. To address this, we non-invasively estimated the density and branching complexity of neurite (dendrites, axons, glial processes) using diffusion-weighted MRI in 364 participants aged 8-21. With development, large increases in neurite density and branching complexity persisted until ~15 years of age before stabilizing at adult-like values. Neurite density increases were relatively homogenous across hippocampal axes, whereas branching-complexity increases were heterogeneous: increasing primarily in CA1, SRLM, subiculum, and anterior hippocampus. To assess whether this development may be attributable to specific cell-types, we tested for spatial overlap between age-related change in neurite and cell-type composition of the adult hippocampus via cross-reference with an out-of-sample gene-expression atlas. We found age-related changes in neurite density occur in hippocampal locations which, in adults, consist of granule cells, whereas age-related changes in neurite branching complexity occur in locations consisting of pyramidal neurons. These results provide the first glimpse at the nonlinear maturation of hippocampal microstructure and the cell-type composition of hippocampal tissue underlying these changes.