Age-dependent cortical overconnectivity in Shank3 mice is reversed by anesthesia
Abstract Growing evidence points to brain network dysfunction as a central neurobiological basis for autism spectrum disorders (ASDs). As a result, studies on Functional Connectivity (FC) have become pivotal for understanding the large-scale network alterations associated with ASD. Despite ASD being...
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| Language: | English |
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Nature Publishing Group
2025-04-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-025-03377-5 |
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| author | Elena Montagni Manuel Ambrosone Alessandra Martello Lorenzo Curti Federica Polverini Laura Baroncelli Guido Mannaioni Francesco Saverio Pavone Alessio Masi Anna Letizia Allegra Mascaro |
| author_facet | Elena Montagni Manuel Ambrosone Alessandra Martello Lorenzo Curti Federica Polverini Laura Baroncelli Guido Mannaioni Francesco Saverio Pavone Alessio Masi Anna Letizia Allegra Mascaro |
| author_sort | Elena Montagni |
| collection | DOAJ |
| description | Abstract Growing evidence points to brain network dysfunction as a central neurobiological basis for autism spectrum disorders (ASDs). As a result, studies on Functional Connectivity (FC) have become pivotal for understanding the large-scale network alterations associated with ASD. Despite ASD being a neurodevelopmental disorder, and FC being significantly influenced by the brain state, existing FC studies in mouse models predominantly focus on adult subjects under anesthesia. The differential impact of anesthesia and age on cortical functional networks in ASD subjects remains unexplored. To fill this gap, we conducted a longitudinal evaluation of FC across three brain states and three ages in the Shank3b mouse model of autism. We utilized wide-field calcium imaging to monitor cortical activity in Shank3b+/− and Shank3b+/+ mice from late development (P45) through adulthood (P90), and isoflurane anesthesia to manipulate the brain state. Our findings reveal that network hyperconnectivity, emerging from the barrel-field cortices during the juvenile stage, progressively expands to encompass the entire dorsal cortex in adult Shank3b+/− mice. Notably, the severity of FC imbalance is highly dependent on the brain state: global network alterations are more pronounced in the awake state and are strongly reduced under anesthesia. These results underscore the crucial role of anesthesia in detecting autism-related FC alterations and identify a significant network of early cortical dysfunction associated with autism. This network represents a potential target for non-invasive translational treatments. |
| format | Article |
| id | doaj-art-ef2f5554e4c34b68b4205a3029f9f9ae |
| institution | DOAJ |
| issn | 2158-3188 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj-art-ef2f5554e4c34b68b4205a3029f9f9ae2025-08-20T03:18:28ZengNature Publishing GroupTranslational Psychiatry2158-31882025-04-0115111110.1038/s41398-025-03377-5Age-dependent cortical overconnectivity in Shank3 mice is reversed by anesthesiaElena Montagni0Manuel Ambrosone1Alessandra Martello2Lorenzo Curti3Federica Polverini4Laura Baroncelli5Guido Mannaioni6Francesco Saverio Pavone7Alessio Masi8Anna Letizia Allegra Mascaro9Neuroscience Institute, National Research CouncilNeuroscience Institute, National Research CouncilNeuroscience Institute, National Research CouncilDepartment of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of FlorenceDepartment of Health Sciences (DSS), University of FlorenceNeuroscience Institute, National Research CouncilDepartment of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of FlorenceEuropean Laboratory for Non-Linear SpectroscopyDepartment of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of FlorenceNeuroscience Institute, National Research CouncilAbstract Growing evidence points to brain network dysfunction as a central neurobiological basis for autism spectrum disorders (ASDs). As a result, studies on Functional Connectivity (FC) have become pivotal for understanding the large-scale network alterations associated with ASD. Despite ASD being a neurodevelopmental disorder, and FC being significantly influenced by the brain state, existing FC studies in mouse models predominantly focus on adult subjects under anesthesia. The differential impact of anesthesia and age on cortical functional networks in ASD subjects remains unexplored. To fill this gap, we conducted a longitudinal evaluation of FC across three brain states and three ages in the Shank3b mouse model of autism. We utilized wide-field calcium imaging to monitor cortical activity in Shank3b+/− and Shank3b+/+ mice from late development (P45) through adulthood (P90), and isoflurane anesthesia to manipulate the brain state. Our findings reveal that network hyperconnectivity, emerging from the barrel-field cortices during the juvenile stage, progressively expands to encompass the entire dorsal cortex in adult Shank3b+/− mice. Notably, the severity of FC imbalance is highly dependent on the brain state: global network alterations are more pronounced in the awake state and are strongly reduced under anesthesia. These results underscore the crucial role of anesthesia in detecting autism-related FC alterations and identify a significant network of early cortical dysfunction associated with autism. This network represents a potential target for non-invasive translational treatments.https://doi.org/10.1038/s41398-025-03377-5 |
| spellingShingle | Elena Montagni Manuel Ambrosone Alessandra Martello Lorenzo Curti Federica Polverini Laura Baroncelli Guido Mannaioni Francesco Saverio Pavone Alessio Masi Anna Letizia Allegra Mascaro Age-dependent cortical overconnectivity in Shank3 mice is reversed by anesthesia Translational Psychiatry |
| title | Age-dependent cortical overconnectivity in Shank3 mice is reversed by anesthesia |
| title_full | Age-dependent cortical overconnectivity in Shank3 mice is reversed by anesthesia |
| title_fullStr | Age-dependent cortical overconnectivity in Shank3 mice is reversed by anesthesia |
| title_full_unstemmed | Age-dependent cortical overconnectivity in Shank3 mice is reversed by anesthesia |
| title_short | Age-dependent cortical overconnectivity in Shank3 mice is reversed by anesthesia |
| title_sort | age dependent cortical overconnectivity in shank3 mice is reversed by anesthesia |
| url | https://doi.org/10.1038/s41398-025-03377-5 |
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