Harry Alexander Chandler Carey

• Puchades, Maja; Yates, Sharon Christine; Csucs, Gergely; Carey, Harry Alexander Chandler; Balkir, Arda & Leergaard, Trygve B. [Show all 7 contributors for this article] (2025). Software and pipelines for registration and analyses of rodent brain image data in reference atlas space. Frontiers in Neuroinformatics. 19, p. 1–15. doi: 10.3389/fninf.2025.1629388. Full text in Research Archive Show summary

  Advancements in methodologies for efficient large-scale acquisition of high-resolution serial microscopy image data have opened new possibilities for experimental studies of cellular and subcellular features across whole brains in animal models. There is a high demand for open-source software and workflows for automated or semi-automated analysis of such data, facilitating anatomical, functional, and molecular mapping in healthy and diseased brains. These studies share a common need to consistently identify, visualize, and quantify the location of observations within anatomically defined regions, ensuring reproducible interpretation of anatomical locations, and thereby allowing meaningful comparisons of results across multiple independent studies. Addressing this need, we have developed a suite of desktop and web-applications for registration of serial brain section images to three-dimensional brain reference atlases (QuickNII, VisuAlign, WebAlign, WebWarp, and DeepSlice) and for performing data analysis in a spatial context provided by an atlas (Nutil, QCAlign, SeriesZoom, LocaliZoom, and MeshView). The software can be utilized in various combinations, creating customized analytical pipelines suited to specific research needs. The web-applications are integrated in the EBRAINS research infrastructure and coupled to the EBRAINS data platform, establishing the foundation for an online analytical workbench. We here present our software ecosystem, exemplify its use by the research community, and discuss possible directions for future developments.

• Carey, Harry Alexander Chandler; Kleven, Heidi; Øvsthus, Martin; Yates, Sharon Christine; Csucs, Gergely & Puchades, Maja A. [Show all 10 contributors for this article] (2025). DeMBA: a developmental atlas for navigating the mouse brain in space and time. Nature Communications. 16. doi: 10.1038/s41467-025-63177-9. Full text in Research Archive Show summary

  Studies of the adult mouse brain have benefited from three-dimensional (3D) atlases providing standardised frameworks for data analysis and integration. However, few 3D atlases exist for the developing mouse brain, and none cover more than a few ages. This fails to represent the dynamic nature of development and is insufficient for researchers whose data fall between the ages of existent atlases. Existing atlases also neglect the spatial correspondence between ages, making comparison across ages difficult. We present the Developmental Mouse Brain Atlas (DeMBA), a 4D atlas encompassing every postnatal day from 4 to 56. DeMBA was created by using existing brain templates for six developmental time points and interpolating intermediate ages. DeMBA is incorporated in software for spatial registration and analysis, enabling brain-wide quantification of features of interest. Furthermore, we provide the software package CCF translator, allowing coordinates or image volumes to be transformed between ages for comparison. These resources provide age-specific spatial frameworks incorporated in accessible analytic pipelines for developmental mouse brain data.

• Bjerke, Ingvild Elise; Carey, Harry Alexander Chandler; Bjaalie, Jan G.; Leergaard, Trygve B. & Kim, Jee Hyun (2025). The developing mouse dopaminergic system: Cortical-subcortical shift in D1/D2 receptor balance and increasing regional differentiation. Neurochemistry International. ISSN 0197-0186. 182. doi: 10.1016/j.neuint.2024.105899. Full text in Research Archive Show summary

  The dopaminergic system of the brain is involved in complex cognitive functioning and undergoes extensive reorganization during development. Yet, these changes are poorly characterized. We have quantified the density of dopamine 1- and 2-receptor (D1 and D2) positive cells across the forebrain of male and female mice at five developmental stages using validated transgenic mice expressing green fluorescent protein in cells producing D1 or D2 mRNA. After analyzing >4,500 coronal brain images, a cortico-subcortical shift in D1/D2 balance was discovered, with increasing D1 dominance in cortical regions as a maturational pattern that occurs earlier in females. We describe postnatal trajectories of D1 and D2 cell densities across major brain regions and observe increasing regional differentiation of D1 densities through development. Our results provide the most comprehensive overview of the developing dopaminergic system to date, and an empirical foundation for further experimental and computational investigations of dopaminergic signaling.

• Carey, Harry Alexander Chandler; Kleven, Heidi; Øvsthus, Martin; Yates, Sharon Christine; Csucs, Gergely & Puchades, Maja [Show all 9 contributors for this article] (2024). DeMBA: a developmental atlas for navigating the mouse brain in space and time. bioRxiv. ISSN 2692-8205. doi: 10.1101/2024.06.14.598876. Full text in Research Archive Show summary

  Studies of the adult mouse brain have benefited from three-dimensional (3D) atlases providing standardised frameworks for data analysis and integration. However, few 3D atlases exist for the developing mouse brain, and none cover more than a few ages. This fails to represent the dynamic nature of development and is insufficient for researchers whose data fall between the ages of existent atlases. Existing atlases also neglect the spatial correspondence between ages, making comparison across ages difficult. We present the Developmental Mouse Brain Atlas (DeMBA), a 4D atlas encompassing every postnatal day from 4 to 56. DeMBA was created by using existing brain templates for six developmental time points and interpolating intermediate ages. DeMBA is incorporated in software for spatial registration and analysis, enabling brain-wide quantification of features of interest. Furthermore, we provide the software package CCF translator, allowing coordinates or image volumes to be transformed between ages for comparison. These resources provide age-specific spatial frameworks incorporated in accessible analytic pipelines for developmental mouse brain data.

• Bjerke, Ingvild Elise; Yates, Sharon Christine; Carey, Harry; Bjaalie, Jan G. & Leergaard, Trygve B. (2023). Scaling up cell-counting efforts in neuroscience through semi-automated methods. iScience. 26(9). doi: 10.1016/j.isci.2023.107562. Full text in Research Archive Show summary

  Quantifying how the cellular composition of brain regions vary across development, aging, sex, and disease, is crucial in experimental neuroscience, and the accuracy of different counting methods is continuously debated. Due to the tedious nature of most counting procedures, studies are often restricted to one or a few brain regions. Recently, there have been considerable methodological advances in combining semi-automated feature extraction with brain atlases for cell quantification. Such methods hold great promise for scaling up cell-counting efforts. However, little focus has been paid to how these methods should be implemented and reported to support reproducibility. Here, we provide an overview of practices for conducting and reporting cell counting in mouse and rat brains, showing that critical details for interpretation are typically lacking. We go on to discuss how novel methods may increase efficiency and reproducibility of cell counting studies. Lastly, we provide practical recommendations for researchers planning cell counting.

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• Puchades, Maja; Bjerke, Ingvild Elise; Carey, Harry Alexander Chandler; Kleven, Heidi; Øvsthus, Martin & Yates, Sharon Christine [Show all 10 contributors for this article] (2025). QUINT workflow now supports whole brain analysis using the Developmental Mouse Brain Atlas (DeMBA). Full text in Research Archive Show summary

  INTRODUCTION: Three-dimensional, open access digital brain atlases are important resources in neuroscience research, opening new possibilities for automated analyses in atlas defined regions of interest. The EBRAINS QUINT workflow [1,2] has been developed to support standardized atlas-based analysis of sectioned tissue without the need for coding ability. It features integrated brain atlases for the adult rat and mouse brain and is increasingly used in the neuroscience community. However, a recurrent request from many QUINT users interested in understanding brain development, has been to include brain atlases representing different developmental ages, to so achieve better spatial registration for brains from young individuals. METHODS: To meet this need, we have now integrated the novel Developmental Mouse Brain Atlas (DeMBA), a four-dimensional atlas covering every postnatal day from 4 to 56 [3]. This atlas features segmentations from the widely adopted Allen Mouse Brain CCF and the Kim developmental atlases, that have been transformed and interpolated to the same ages, ensuring comparable region definitions across ages [4]. RESULTS AND DISCUSSION: The DeMBA atlas was implemented in the registration software QuickNII and VisuAlign and shared as specific packages together with the atlas itself on EBRAINS [4]. Those versions require usage of the specific Filebuilder utility shared within the packages. Next, the DeMBA atlas was implemented in a new Nutil Quantifier version (v1.1) and thereby the complete QUINT analysis can now be performed on young mouse brains. All the software tools and the DeMBA atlas are shared through the EBRAINS Knowledge graph [5]. We here present the updated QUINT workflow and give examples of preliminary developmental data analysis. References: 1.Yates, S. et al. (2019) QUINT: Workflow for Quantification and Spatial Analysis of Features in Histological Images From Rodent Brain. Front. Neuroinform. 13, 1–14. https://doi.org/10.3389/fninf.2019.00075 2. Puchades MA, Yates SC, Csucs G, Carey H, Balkir A, Leergaard TB and Bjaalie JG (2025) Software and pipelines for registration and analyses of rodent brain image data in reference atlas space. Front. Neuroinform. 19:1629388. https://doi.org/10.3389/fninf.2025.1629388 3.Carey, H., Ovsthus, M., Kleven, H., Yates, S. C., Csucs, G., Puchades, M. A., Bjaalie, J. G., Leergaard, T. B., & Bjerke, I. E. (2024). Developmental mouse brain atlas (DeMBA) with continuous coverage of postnatal day 4 to 56 (v1) [Data set]. EBRAINS. https://doi.org/10.25493/V3AH-HK7 4.Carey, H., Kleven, H., Øvsthus, M. et al. DeMBA: a developmental atlas for navigating the mouse brain in space and time. Nat Commun 16, 8108 (2025). https://doi.org/10.1038/s41467-025-63177-9 5.https://search.kg.ebrains.eu Acknowledgeme

• Kleven, Heidi; Øvsthus, Martin; Carey, Harry Alexander Chandler; Puchades, Maja; Bjaalie, Jan G. & Leergaard, Trygve B. [Show all 7 contributors for this article] (2024). Three-dimensional reference atlases for integration and analysis of data from the postnatal mouse brain. Full text in Research Archive
• Puchades, Maja Amedjkouh; Yates, Sharon Christine; Bjerke, Ingvild Elise & Carey, Harry (2023). Rodent atlasing tools and the QUINT workflow. Full text in Research Archive

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