[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-450204-105":59,"doc-detail-450204-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","a-chromosome-region-linked-to-neurodevelopmental-disorders-influences-locomotor-behavior-through-sex-specific-neural-circuits-research-article","A chromosome region linked to neurodevelopmental disorders influences locomotor behavior through sex-specific neural circuits - Research article","","Biological sex modulates the expression and progression of neurodevelopmental disorders, yet the mechanisms remain unclear. This study examines 16p11.2 hemideletion (16p11.2 del/+), a genetic risk factor for NDDs, using snRNA-seq to reveal sex- and cell type-specific transcriptomic changes in D1- and D2-spiny projection neurons, with stronger effects in males. Fiber photometry shows reduced dorsal striatal activity in males, driven mainly by D2-SPNs, while conditional deletions induce sex-specific hyperactivity patterns.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/a-chromosome-region-linked-to-neurodevelopmental-disorders-influences-locomotor-behavior-through-sex-specific-neural-circuits-research-article/450204/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/a-chromosome-region-linked-to-neurodevelopmental-disorders-influences-locomotor-behavior-through-sex-specific-neural-circuits-research-article/450204.png","ImageObject",300,407,{"name":92,"@type":93},"Ezra","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-07","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What genetic factor is studied in relation to neurodevelopmental disorders?","Question",{"text":112,"@type":113},"The study focuses on 16p11.2 hemideletion (16p11.2 del/+), a rare chromosomal hemideletion within the 16p11.2 locus and a common genetic risk factor for NDDs.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do the results link sex to locomotor-related neural activity?",{"text":117,"@type":113},"Reduced dorsal striatal neuronal activity is observed in 16p11.2 del/+ males but not females, indicating sex-specific circuit effects relevant to locomotor behavior.",{"name":119,"@type":110,"acceptedAnswer":120},"Which striatal neuron type is identified as the main contributor to the male-specific activity reduction?",{"text":121,"@type":113},"D2-spiny projection neurons (D2-SPNs) are identified as the primary contributors to the reduced dorsal striatal activity seen in males.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},450204,1790819799,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},1099514068035,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Article [https://doi.org/10.1038/s41467-025-68047-y](https://doi.org/10.1038/s41467-025-68047-y)  \nA chromosome region linked toneurodevelopmental disorders influences locomotor behavior through sex-specific neural circuits  \nReceived: 30 April 2024  \n\n| Accepted: 16 December 2025 |\n| --- |\n| |\n| Check for updates |\n\nJaekyoon Kim 1,2, Yann Vanrobaeys 1,2,3, Remya Rajan4,  \nM. Felicia Davatolhagh5, Benjamin Kelvington 1,2, Snehajyoti Chatterjee 1,2, Sarah L. Ferri2,6, Christopher Angelakos7, Alea A. Mills8, Marc V. Fuccillo 9, Kim T. Blackwell 4, Thomas Nickl-Jockschat 10,11,12 & Ted Abel 1,2,13   \nBiological sex shapes the manifestation and progression of neurodevelopmental disorders (NDDs), however, the underlying mechanisms remains unclear. Hemideletion of the 16p11.2 region (16p11.2 del/+) is associated with NDDs, and 16p11.2 del/+ mice exhibit sex-specific, striatum-related phenotypes relevant to NDDs. In this study, using snRNA-seq, we identify cell type-and sexspecific transcriptomic changes in D1-and D2-spiny projection neurons (SPNs), with greater impact in males. Fiber photometry recordings reveal reduced neuronal activity in the dorsal striatum of 16p11.2 del/+ males, but not females, with D2-SPNs identified as the primary contributors to this reduction. Behaviorally, we utilize conditional genetic approaches and find that selective hemideletion in D2-SPNs, but not D1-SPNs, induces male-specific hyperactivity, whereas cortical hemideletion increases hyperactivity in both sexes. Thus, a locus linked to NDDs acts in distinct striatal circuits, selectively impacting behavior in a sex-and cell type-specific manner.  \nMale and female brains differ fundamentally in their reaction to genetic risk for brain disorders1. Sex differences in incidence, symptom presentation, and outcome have been found across biologically heterogeneous disorders, ranging from affective disorders to neurodegenerative diseases and primary brain tumors2–4. Neurodevelopmental disorders (NDDs), including autism spectrum disorders (ASD) and  \nattention-deficit hyperactivity disorder (ADHD), provide a particularly striking example of sex-specific vulnerability, with male-to-female ratios of 4:1 ASD and 2:1 for ADHD5,6. Although the primary features of ASD are consistent across sexes, females can present differently than males, exhibiting fewer or harder-to-detect behavioral alterations7,8. This bias is most likely driven by a differential vulnerability of distinct  \n1Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA. 2Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA. 3Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA, USA. 4Roy J. Carver Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA. 5Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. 6Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA. 7Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA. 8Cold Spring Harbor Laboratory, Cold Spring Harbor, Laurel Hollow, NY, USA. 9Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA. 10Department of Psychiatry and Psychotherapy, Otto von Guericke University Magdeburg, Magdeburg, Germany. 11German Center for Mental Health (DZPG), partner site Halle-Jena-Magdeburg, Berlin, Germany. 12Center for Intervention and Research on adaptive and maladaptive brain Circuits underlying mental health (C-I-R-C), Halle-Jena-Magdeburg, Germany. 13Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA. e-mail: [ted-abel@uiowa.edu](ted-abel@uiowa.edu)  \nneuronal circuits to genetic risk factors9,10, but identifying the exact underlying mechanisms remains a major challenge in the field.  \nMultiple lines of evidence have ","cbCaicUlHlX0yjOe","https://ap.wps.com/l/cbCaicUlHlX0yjOe","pdf",2730318,17,"English","# Background and rationale\n## Sex differences in neurodevelopmental disorders\n## Striatal circuits and locomotor regulation\n# Study aims and model\n## 16p11.2 hemideletion and CNV risk\n# Experimental approach (overview)\n## snRNA-seq and transcriptomic changes\n## Fiber photometry and neuronal activity\n## Conditional genetic manipulations and behavior","[{\"question\":\"What genetic factor is studied in relation to neurodevelopmental disorders?\",\"answer\":\"The study focuses on 16p11.2 hemideletion (16p11.2 del/+), a rare chromosomal hemideletion within the 16p11.2 locus and a common genetic risk factor for NDDs.\"},{\"question\":\"How do the results link sex to locomotor-related neural activity?\",\"answer\":\"Reduced dorsal striatal neuronal activity is observed in 16p11.2 del/+ males but not females, indicating sex-specific circuit effects relevant to locomotor behavior.\"},{\"question\":\"Which striatal neuron type is identified as the main contributor to the male-specific activity reduction?\",\"answer\":\"D2-spiny projection neurons (D2-SPNs) are identified as the primary contributors to the reduced dorsal striatal activity seen in males.\"}]","A chromosome region linked to neurodevelopmental disorders influences locomotor behavior through sex-specific neural circuits - Research article | PDF",1790732440,43]