Abstract
The subiculum is the major output component of the hippocampal formation and one of the major brain structures most affected by Alzheimer’s disease. Our previous work revealed a hidden laminar architecture within the mouse subiculum. However, the rotation of the hippocampal longitudinal axis across species makes it unclear how the laminar organization is represented in human subiculum. Using in situ hybridization data from the Allen Human Brain Atlas, we demonstrate that the human subiculum also contains complementary laminar gene expression patterns similar to the mouse. In addition, we provide evidence that the molecular domain boundaries in human subiculum correspond to microstructural differences observed in high resolution MRI and fiber density imaging. Finally, we show both similarities and differences in the gene expression profile of subiculum pyramidal cells within homologous lamina. Overall, we present a new 3D model of the anatomical organization of human subiculum and its evolution from the mouse.
Highlights
The subiculum is the major output component of the hippocampal formation and one of the major brain structures most affected by Alzheimer’s disease
Our previous work creating the Hippocampus Gene Expression Atlas (HGEA) demonstrated that combinatorial gene expression patterns identify the hidden sublaminar organization of SUB pyramidal neurons and these gene expression patterns were highly related to specific connectivity labeling p atterns[6]
Similar to the approach used by Lorente de Nó previously, the HGEA outlines five SUB subregions based on the representation of four identified gene expression lamina: dorsal and ventral parts of the dorsal subiculum (SUBdd and SUBdv, respectively), the prosubiculum (ProSUB), and the ventral subiculum (SUBv) along with its ventral tip (SUBvv)
Summary
The subiculum is the major output component of the hippocampal formation and one of the major brain structures most affected by Alzheimer’s disease. We provide evidence that the molecular domain boundaries in human subiculum correspond to microstructural differences observed in high resolution MRI and fiber density imaging We show both similarities and differences in the gene expression profile of subiculum pyramidal cells within homologous lamina. Based on the anatomical and functional homology, we hypothesized that the laminar gene expression patterns that delineate mouse HGEA SUB subregions would demonstrate a similar relationship pattern in the corresponding parts of human SUB. In the anterior SUB, we found these lamina continued within ventral parts of the SUB, but not in the dorsal parts of the anterior SUB, suggesting a difference between dorsal and ventral parts of the anterior SUB that was not previously known Taking this new data together with our previous understanding of the mouse subiculum, we propose a new 3D model of the human subiculum and its homology to the rodent. Our gene expression analysis provides a new understanding of the homology between mouse and human hippocampus that is critical to translational studies of hippocampal diseases such as Alzheimer’s disease, hippocampal sclerosis, and epilepsy
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