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Peer-reviewedCC BY 4.0Hippocampus

Quantitative Assessment of Mesoscale Cellular Order and Organization in the Mouse Hippocampus

  • Konstantin Hein1,2,3,4,5,6
  • Humberto Romero‐Limon1,2,3,6
  • Conrad Möckel1,2,5
  • Anne Karasinsky4
  • Stephanie Möllmert1,2
  • Jona Kayser1,2,5
  • Alessio Zaccone7
  • Jochen Guck1,2,5
  • Tomohisa Toda1,3,4,6
7 affiliations
  1. 1Max‐Planck‐Zentrum für Physik und Medizin Erlangen Germany
  2. 2Max Planck Institute for the Science of Light Erlangen Germany
  3. 3Faculty of Medicine, Laboratory of Neural Epigenomics, Medical Institute of Biophysics Friedrich‐Alexander Universität Erlangen‐Nürnberg Erlangen Germany
  4. 4Nuclear Architecture in Neural Plasticity and Aging German Center for Neurodegenerative Diseases (DZNE) Dresden Germany
  5. 5Department of Physics, Institute of Optics, Information and Photonics FAU Erlangen Germany
  6. 6Department of Stem Cell Biology University Hospital Erlangen, Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Erlangen Germany
  7. 7Department of Physics “A. Pontremoli” University of Milan and INFN Milan Italy
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Abstract

The hippocampus is characterized by a stereotypical macroscopic structure, where the nuclei are densely and heterogeneously packed among different subregions of the hippocampus. Despite the fact that tissue‐specific cellular organization has been implicated in neural function, it has been technically challenging to quantitatively analyze mesoscopic cellular organization in the hippocampus due to its high cellular density. To overcome this technical hurdle, we developed Computational Biophysical Histomorphometry Software (CBHS), an automated image‐analysis pipeline aimed at quantifying nuclear shape and the order of the cellular ensemble in high‐density areas. When applied to the subfields of the hippocampus, we found that denser regions, most notably the dentate gyrus, were the most positionally, but least orientationally ordered. Nuclear shape exhibited a dependence on the local environment in a packing‐dependent manner. This association was cell‐type specific, with neurons, but not astrocytes displaying nuclear shape that varied with neighbor proximity, although astrocytes demonstrated greater intrinsic shape variance. The results reveal the presence of reproducible mesoscale cell packing order in hippocampal tissue, and are consistent with a nucleus‐driven mechanical coupling between neighboring cells. The present study provides a quantitative framework with which to understand mesoscopic tissue organization, thus enabling the formulation of testable hypotheses for future investigation.

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Cite

BibTeXRIS
BibTeX
@article{hein2026quantitative,
  title = {{Quantitative Assessment of Mesoscale Cellular Order and Organization in the Mouse Hippocampus}},
  author = {Konstantin Hein and Humberto Romero‐Limon and Conrad Möckel and Anne Karasinsky and Stephanie Möllmert and Jona Kayser and Alessio Zaccone and Jochen Guck and Tomohisa Toda},
  journal = {Hippocampus},
  year = {2026},
  month = oct,
  doi = {10.1002/hipo.70139},
  url = {https://doi.org/10.1002/hipo.70139},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Quantitative Assessment of Mesoscale Cellular Order and Organization in the Mouse Hippocampus
AU  - Konstantin Hein
AU  - Humberto Romero‐Limon
AU  - Conrad Möckel
AU  - Anne Karasinsky
AU  - Stephanie Möllmert
AU  - Jona Kayser
AU  - Alessio Zaccone
AU  - Jochen Guck
AU  - Tomohisa Toda
PY  - 2026
DA  - 2026/10/26
JO  - Hippocampus
DO  - 10.1002/hipo.70139
UR  - https://doi.org/10.1002/hipo.70139
AB  - The hippocampus is characterized by a stereotypical macroscopic structure, where the nuclei are densely and heterogeneously packed among different subregions of the hippocampus. Despite the fact that tissue‐specific cellular organization has been implicated in neural function, it has been technically challenging to quantitatively analyze mesoscopic cellular organization in the hippocampus due to its high cellular density. To overcome this technical hurdle, we developed Computational Biophysical Histomorphometry Software (CBHS), an automated image‐analysis pipeline aimed at quantifying nuclear shape and the order of the cellular ensemble in high‐density areas. When applied to the subfields of the hippocampus, we found that denser regions, most notably the dentate gyrus, were the most positionally, but least orientationally ordered. Nuclear shape exhibited a dependence on the local environment in a packing‐dependent manner. This association was cell‐type specific, with neurons, but not astrocytes displaying nuclear shape that varied with neighbor proximity, although astrocytes demonstrated greater intrinsic shape variance. The results reveal the presence of reproducible mesoscale cell packing order in hippocampal tissue, and are consistent with a nucleus‐driven mechanical coupling between neighboring cells. The present study provides a quantitative framework with which to understand mesoscopic tissue organization, thus enabling the formulation of testable hypotheses for future investigation.
SN  - 1050-9631
SN  - 1098-1063
ER  -