Syngap1 promotes cognitive function through regulation of cortical sensorimotor dynamics
Abstract Perception, a cognitive construct, emerges through sensorimotor integration (SMI). The genetic mechanisms that shape SMI required for perception are unknown. Here, we demonstrate in mice that expression of the autism/intellectual disability gene, Syngap1, in cortical excitatory neurons is r...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56125-0 |
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| author | Thomas Vaissiere Sheldon D. Michaelson Thomas Creson Jessie Goins Daniel Fürth Diana Balazsfi Camilo Rojas Randall Golovin Konstantinos Meletis Courtney A. Miller Daniel O’Connor Lorenzo Fontolan Gavin Rumbaugh |
| author_facet | Thomas Vaissiere Sheldon D. Michaelson Thomas Creson Jessie Goins Daniel Fürth Diana Balazsfi Camilo Rojas Randall Golovin Konstantinos Meletis Courtney A. Miller Daniel O’Connor Lorenzo Fontolan Gavin Rumbaugh |
| author_sort | Thomas Vaissiere |
| collection | DOAJ |
| description | Abstract Perception, a cognitive construct, emerges through sensorimotor integration (SMI). The genetic mechanisms that shape SMI required for perception are unknown. Here, we demonstrate in mice that expression of the autism/intellectual disability gene, Syngap1, in cortical excitatory neurons is required for the formation of somatomotor networks that promote SMI-mediated perception. Cortical Syngap1 expression was necessary and sufficient for setting tactile sensitivity, sustaining tactile object exploration, and promoting tactile learning. Mice with deficient Syngap1 expression exhibited impaired neural dynamics induced by exploratory touches within a cortical-thalamic network that promotes attention and perception. Disrupted neuronal dynamics were associated with circuit-specific long-range synaptic connectivity abnormalities. Our data support a model where autonomous Syngap1 expression in cortical excitatory neurons promotes cognitive abilities through the assembly of long-range circuits that integrate temporally-overlapping sensory and motor signals, a process that promotes perception and attention. These data provide systems-level insights into the robust association between Syngap1 expression and cognitive ability. |
| format | Article |
| id | doaj-art-dc07542dbfac4aa89943ae0f44fa9d95 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-dc07542dbfac4aa89943ae0f44fa9d952025-01-19T12:30:41ZengNature PortfolioNature Communications2041-17232025-01-0116112310.1038/s41467-025-56125-0Syngap1 promotes cognitive function through regulation of cortical sensorimotor dynamicsThomas Vaissiere0Sheldon D. Michaelson1Thomas Creson2Jessie Goins3Daniel Fürth4Diana Balazsfi5Camilo Rojas6Randall Golovin7Konstantinos Meletis8Courtney A. Miller9Daniel O’Connor10Lorenzo Fontolan11Gavin Rumbaugh12Department of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & TechnologyDepartment of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & TechnologyDepartment of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & TechnologyDepartment of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & TechnologySciLifeLab, Department of Immunology, Genetics & Pathology, Uppsala UniversityDepartment of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & TechnologyDepartment of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & TechnologyDepartment of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & TechnologyDepartment of Neuroscience, Karolinska InstituteDepartment of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & TechnologyDepartment of Neuroscience, The Johns Hopkins University School of MedicineAix-Marseille Université, INSERM, INMED, Turing Centre for Living SystemsDepartment of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & TechnologyAbstract Perception, a cognitive construct, emerges through sensorimotor integration (SMI). The genetic mechanisms that shape SMI required for perception are unknown. Here, we demonstrate in mice that expression of the autism/intellectual disability gene, Syngap1, in cortical excitatory neurons is required for the formation of somatomotor networks that promote SMI-mediated perception. Cortical Syngap1 expression was necessary and sufficient for setting tactile sensitivity, sustaining tactile object exploration, and promoting tactile learning. Mice with deficient Syngap1 expression exhibited impaired neural dynamics induced by exploratory touches within a cortical-thalamic network that promotes attention and perception. Disrupted neuronal dynamics were associated with circuit-specific long-range synaptic connectivity abnormalities. Our data support a model where autonomous Syngap1 expression in cortical excitatory neurons promotes cognitive abilities through the assembly of long-range circuits that integrate temporally-overlapping sensory and motor signals, a process that promotes perception and attention. These data provide systems-level insights into the robust association between Syngap1 expression and cognitive ability.https://doi.org/10.1038/s41467-025-56125-0 |
| spellingShingle | Thomas Vaissiere Sheldon D. Michaelson Thomas Creson Jessie Goins Daniel Fürth Diana Balazsfi Camilo Rojas Randall Golovin Konstantinos Meletis Courtney A. Miller Daniel O’Connor Lorenzo Fontolan Gavin Rumbaugh Syngap1 promotes cognitive function through regulation of cortical sensorimotor dynamics Nature Communications |
| title | Syngap1 promotes cognitive function through regulation of cortical sensorimotor dynamics |
| title_full | Syngap1 promotes cognitive function through regulation of cortical sensorimotor dynamics |
| title_fullStr | Syngap1 promotes cognitive function through regulation of cortical sensorimotor dynamics |
| title_full_unstemmed | Syngap1 promotes cognitive function through regulation of cortical sensorimotor dynamics |
| title_short | Syngap1 promotes cognitive function through regulation of cortical sensorimotor dynamics |
| title_sort | syngap1 promotes cognitive function through regulation of cortical sensorimotor dynamics |
| url | https://doi.org/10.1038/s41467-025-56125-0 |
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