Developmental regression of novel space preference in an autism spectrum disorder model is unlinked to GABAergic and social circuitry
Autism spectrum disorder (ASD) is characterized by social deficits and restricted behaviors, with developmental defects in GABAergic circuits proposed as a key underlying etiology. Here, we introduce the V-Y assay, a novel space preference test in which one arm of the Y-maze is initially hidden and...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2024.1513347/full |
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| author | Hirofumi Asano Hirofumi Asano Masaya Arai Masaya Arai Aito Narita Takayuki Kuroiwa Mamoru Fukuchi Yuhei Yoshimoto Soichi Oya Goichi Miyoshi |
| author_facet | Hirofumi Asano Hirofumi Asano Masaya Arai Masaya Arai Aito Narita Takayuki Kuroiwa Mamoru Fukuchi Yuhei Yoshimoto Soichi Oya Goichi Miyoshi |
| author_sort | Hirofumi Asano |
| collection | DOAJ |
| description | Autism spectrum disorder (ASD) is characterized by social deficits and restricted behaviors, with developmental defects in GABAergic circuits proposed as a key underlying etiology. Here, we introduce the V-Y assay, a novel space preference test in which one arm of the Y-maze is initially hidden and later revealed as a novel space. Using an ASD mouse model with FOXG1 haploinsufficiency, which exhibits ASD-like social impairments that can be either exacerbated or ameliorated by GABAergic circuit manipulations, we observed impaired novel space preference and exploratory behavior in the V-Y assay. Interestingly, unlike social phenotypes, novel space preference was initially established by 3 weeks of age but regressed by 6 weeks. Furthermore, alterations in GABAergic signaling via Gad2 mutation did not affect novel space preference, in contrast to their impact on social behaviors. These findings reveal that the regression of novel space preference in ASD follows a distinct developmental trajectory from GABA-driven social impairments, providing new insights into the mechanisms underlying ASD. |
| format | Article |
| id | doaj-art-0af902c7eaa74c59b4bf222b761274e5 |
| institution | Kabale University |
| issn | 1662-5102 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj-art-0af902c7eaa74c59b4bf222b761274e52025-01-15T10:42:33ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022025-01-011810.3389/fncel.2024.15133471513347Developmental regression of novel space preference in an autism spectrum disorder model is unlinked to GABAergic and social circuitryHirofumi Asano0Hirofumi Asano1Masaya Arai2Masaya Arai3Aito Narita4Takayuki Kuroiwa5Mamoru Fukuchi6Yuhei Yoshimoto7Soichi Oya8Goichi Miyoshi9Department of Developmental Genetics and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Gunma, JapanDepartment of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, JapanDepartment of Developmental Genetics and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Gunma, JapanLaboratory of Molecular Neuroscience, Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Gunma, JapanDepartment of Developmental Genetics and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Gunma, JapanDepartment of Developmental Genetics and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Gunma, JapanLaboratory of Molecular Neuroscience, Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Gunma, JapanDepartment of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, JapanDepartment of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, JapanDepartment of Developmental Genetics and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Gunma, JapanAutism spectrum disorder (ASD) is characterized by social deficits and restricted behaviors, with developmental defects in GABAergic circuits proposed as a key underlying etiology. Here, we introduce the V-Y assay, a novel space preference test in which one arm of the Y-maze is initially hidden and later revealed as a novel space. Using an ASD mouse model with FOXG1 haploinsufficiency, which exhibits ASD-like social impairments that can be either exacerbated or ameliorated by GABAergic circuit manipulations, we observed impaired novel space preference and exploratory behavior in the V-Y assay. Interestingly, unlike social phenotypes, novel space preference was initially established by 3 weeks of age but regressed by 6 weeks. Furthermore, alterations in GABAergic signaling via Gad2 mutation did not affect novel space preference, in contrast to their impact on social behaviors. These findings reveal that the regression of novel space preference in ASD follows a distinct developmental trajectory from GABA-driven social impairments, providing new insights into the mechanisms underlying ASD.https://www.frontiersin.org/articles/10.3389/fncel.2024.1513347/fullGABAergic developmentASD modelnovel space preferenceregressionsocial behavior |
| spellingShingle | Hirofumi Asano Hirofumi Asano Masaya Arai Masaya Arai Aito Narita Takayuki Kuroiwa Mamoru Fukuchi Yuhei Yoshimoto Soichi Oya Goichi Miyoshi Developmental regression of novel space preference in an autism spectrum disorder model is unlinked to GABAergic and social circuitry Frontiers in Cellular Neuroscience GABAergic development ASD model novel space preference regression social behavior |
| title | Developmental regression of novel space preference in an autism spectrum disorder model is unlinked to GABAergic and social circuitry |
| title_full | Developmental regression of novel space preference in an autism spectrum disorder model is unlinked to GABAergic and social circuitry |
| title_fullStr | Developmental regression of novel space preference in an autism spectrum disorder model is unlinked to GABAergic and social circuitry |
| title_full_unstemmed | Developmental regression of novel space preference in an autism spectrum disorder model is unlinked to GABAergic and social circuitry |
| title_short | Developmental regression of novel space preference in an autism spectrum disorder model is unlinked to GABAergic and social circuitry |
| title_sort | developmental regression of novel space preference in an autism spectrum disorder model is unlinked to gabaergic and social circuitry |
| topic | GABAergic development ASD model novel space preference regression social behavior |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2024.1513347/full |
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