{"doi":"10.7554/elife.82376","title":"Sex, strain, and lateral differences in brain cytoarchitecture across a large mouse population","abstract":"<jats:p>The mouse brain is by far the most intensively studied among mammalian brains, yet basic measures of its cytoarchitecture remain obscure. For example, quantifying cell numbers, and the interplay of sex, strain, and individual variability in cell density and volume is out of reach for many regions. The Allen Mouse Brain Connectivity project produces high-resolution full brain images of hundreds of brains. Although these were created for a different purpose, they reveal details of neuroanatomy and cytoarchitecture. Here, we used this population to systematically characterize cell density and volume for each anatomical unit in the mouse brain. We developed a DNN-based segmentation pipeline that uses the autofluorescence intensities of images to segment cell nuclei even within the densest regions, such as the dentate gyrus. We applied our pipeline to 507 brains of males and females from C57BL/6J and FVB.CD1 strains. Globally, we found that increased overall brain volume does not result in uniform expansion across all regions. Moreover, region-specific density changes are often negatively correlated with the volume of the region; therefore, cell count does not scale linearly with volume. Many regions, including layer 2/3 across several cortical areas, showed distinct lateral bias. We identified strain-specific or sex-specific differences. For example, males tended to have more cells in extended amygdala and hypothalamic regions (MEA, BST, BLA, BMA, and LPO, AHN) while females had more cells in the orbital cortex (ORB). Yet, inter-individual variability was always greater than the effect size of a single qualifier. We provide the results of this analysis as an accessible resource for the community.</jats:p>","journal":"eLife","year":2023,"id":594680,"datarank":0.4636563680037475,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.0,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.0,"corpus_percentile":59.0,"corpus_rank":5335,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1045277,"name":"Hannah Hochgerner","orcid":"0000-0002-7739-666X","position":1,"is_corresponding":false},{"id":1522450,"name":"Etay Aloni","orcid":null,"position":2,"is_corresponding":false},{"id":104688,"name":"Noam Shental","orcid":"0000-0001-9645-3773","position":3,"is_corresponding":false},{"id":78290,"name":"Amit Zeisel","orcid":"0000-0002-2424-9279","position":4,"is_corresponding":false},{"id":1522449,"name":"David Elkind","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Sex, strain, and lateral differences in brain cytoarchitecture across a large mouse population","abstract":"<jats:p>The mouse brain is by far the most intensively studied among mammalian brains, yet basic measures of its cytoarchitecture remain obscure. For example, quantifying cell numbers, and the interplay of sex, strain, and individual variability in cell density and volume is out of reach for many regions. The Allen Mouse Brain Connectivity project produces high-resolution full brain images of hundreds of brains. Although these were created for a different purpose, they reveal details of neuroanatomy and cytoarchitecture. Here, we used this population to systematically characterize cell density and volume for each anatomical unit in the mouse brain. We developed a DNN-based segmentation pipeline that uses the autofluorescence intensities of images to segment cell nuclei even within the densest regions, such as the dentate gyrus. We applied our pipeline to 507 brains of males and females from C57BL/6J and FVB.CD1 strains. Globally, we found that increased overall brain volume does not result in uniform expansion across all regions. Moreover, region-specific density changes are often negatively correlated with the volume of the region; therefore, cell count does not scale linearly with volume. Many regions, including layer 2/3 across several cortical areas, showed distinct lateral bias. We identified strain-specific or sex-specific differences. For example, males tended to have more cells in extended amygdala and hypothalamic regions (MEA, BST, BLA, BMA, and LPO, AHN) while females had more cells in the orbital cortex (ORB). Yet, inter-individual variability was always greater than the effect size of a single qualifier. We provide the results of this analysis as an accessible resource for the community.</jats:p>","is_dataset_classified":null,"base_score":3.091042453358316,"endowment":3.091042453358316,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37144870","pmcid":"PMC10212558","openalex_id":"https://openalex.org/W4372335659","authors":[],"funders":[{"funder_name":"European Research Council","grant_id":"TYPEWIRE-852786","title":null},{"funder_name":"Human Frontier Science Program","grant_id":"CDA-0039/2019-C","title":null},{"funder_name":"Israel Science Foundation","grant_id":"2028912","title":null},{"funder_name":"Israel ministry of science, technology & space","grant_id":"3-16033","title":null},{"funder_name":"European Research Council","grant_id":"852786","title":"Reconstructing wiring rules of in vivo neural networks using simultaneous single-cell connectomics and transcriptomics"},{"funder_name":"Swedish Brain Foundation","grant_id":"","title":null}],"total_grants":6,"fwci":2.7415,"citation_percentile":0.90740643,"influential_citations":0,"citation_trend":[{"year":2023,"count":5},{"year":2024,"count":8},{"year":2025,"count":6},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.7554/elife.82376","host_type":"journal"},{"url":"https://doi.org/10.7554/elife.82376","host_type":"publisher"},{"url":"https://cdn.elifesciences.org/articles/82376/elife-82376-v3.pdf","host_type":"publisher"},{"url":"https://cdn.elifesciences.org/articles/82376/elife-82376-v3.xml","host_type":"publisher"},{"url":"https://elifesciences.org/articles/82376","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37144870","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10212558","host_type":"repository"},{"url":"https://doaj.org/article/8686c8b2da46415fb2ea238a0aea061b","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10212558/pdf/elife-82376.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10212558","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10212558?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1101/2022.08.09.503434","host_type":""},{"url":"http://dx.doi.org/10.7554/eLife.82376","host_type":""}],"fields_of_study":["Photoreceptor and optogenetics research","Circadian rhythm and melatonin","Neural dynamics and brain function","0301 basic medicine","0303 health sciences","03 medical and health sciences","Male","Female","Mice","Animals","Mice, Inbred C57BL","Brain","Neuroanatomy","Amygdala","Sex Characteristics","Mammals"],"mesh_terms":["Amygdala","Animals","Brain","Female","Male","Mammals","Mice, Inbred C57BL","Neuroanatomy","Sex Characteristics","Mice"],"keywords":["Cytoarchitecture","Neuroanatomy","Brain size","Biology","Population","Neuroscience","Brain morphometry","Anatomy","Dentate gyrus","Hippocampus","Magnetic resonance imaging","Mouse","Imaging","systems biology","computational biology","Sexual Dimorphism","Mouse Brain","Male","Mammals","Sex Characteristics","QH301-705.5","Science","Q","R","Brain","Amygdala","Mice, Inbred C57BL","Mice","Medicine","Animals","Female","Biology (General)","Computational and Systems Biology"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T15:14:59.799967Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}