Developmental changes in hippocampal neurite colocalize with the expression of genes involved in modulating low-theta oscillations

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, we observed large increases in neurite density and branching complexity that persisted until approximately 15 years of age before stabilizing at adult-like values. Increases in neurite density were relatively homogenous across hippocampal axes, whereas increases in branching complexity 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 the cell-type composition of hippocampal tissue via cross-reference with an out-of-sample gene-expression atlas. We found age-related changes in neurite density spatially overlapped with a granule cell component; whereas age-related changes in neurite branching complexity overlapped with a pyramidal neuron component. These results provide the first glimpse at the nonlinear maturation of hippocampal microstructure and the cell-type composition of hippocampal tissue underlying these changes.