Kember Jonah, Gracia-Tabuenca Zeus, Patel Raihann, Chakravarty Mallar, Chai Xiaoqian J
Montreal Neurological Institute & Hospital, McGill University, Montréal, QC, H3A 2B4, Canada.
Department of Statistics, University of Zaragoza, C. de Pedro Cerbuna, 12, 50009, Zaragoza, Spain.
Commun Biol. 2025 Feb 25;8(1):302. doi: 10.1038/s42003-025-07725-5.
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.
海马体是支持记忆编码和提取的关键脑结构,但其在人类中的微观结构发育仍不清楚。了解这种发育情况可能有助于深入了解记忆的潜在机制及其在疾病中的破坏情况。为了解决这个问题,我们使用扩散加权磁共振成像对364名8至21岁的参与者进行了非侵入性估计,以评估神经突(树突、轴突、胶质突起)的密度和分支复杂性。随着发育,神经突密度和分支复杂性大幅增加,这种情况一直持续到约15岁,之后稳定在类似成人的水平。神经突密度的增加在海马体各轴上相对均匀,而分支复杂性的增加则是不均匀的:主要在CA1、SRLM、海马下托和海马前部增加。为了评估这种发育是否可能归因于特定的细胞类型,我们通过与样本外基因表达图谱交叉参考,测试了神经突年龄相关变化与成年海马体细胞类型组成之间的空间重叠。我们发现,神经突密度的年龄相关变化发生在海马体中成年时由颗粒细胞组成的区域,而神经突分支复杂性的年龄相关变化发生在由锥体神经元组成的区域。这些结果首次揭示了海马体微观结构的非线性成熟以及这些变化背后海马体组织的细胞类型组成。