Cortex-restricted deletion of Foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autism
Abstract Background Many children and young people with autism spectrum disorder (ASD) display touch defensiveness or avoidance (hypersensitivity), or engage in sensory seeking by touching people or objects (hyposensitivity). Abnormal sensory responses have also been noticed in mice lacking ASD-asso...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Molecular Autism |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13229-023-00567-0 |
| _version_ | 1797559273242230784 |
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| author | Xue Li Shishuai Hao Shimin Zou Xiaomeng Tu Weixi Kong Tian Jiang Jie-Guang Chen |
| author_facet | Xue Li Shishuai Hao Shimin Zou Xiaomeng Tu Weixi Kong Tian Jiang Jie-Guang Chen |
| author_sort | Xue Li |
| collection | DOAJ |
| description | Abstract Background Many children and young people with autism spectrum disorder (ASD) display touch defensiveness or avoidance (hypersensitivity), or engage in sensory seeking by touching people or objects (hyposensitivity). Abnormal sensory responses have also been noticed in mice lacking ASD-associated genes. Tactile sensory information is normally processed by the somatosensory system that travels along the thalamus to the primary somatosensory cortex. The neurobiology behind tactile sensory abnormalities, however, is not fully understood. Methods We employed cortex-specific Foxp1 knockout (Foxp1-cKO) mice as a model of autism in this study. Tactile sensory deficits were measured by the adhesive removal test. The mice’s behavior and neural activity were further evaluated by the whisker nuisance test and c-Fos immunofluorescence, respectively. We also studied the dendritic spines and barrel formation in the primary somatosensory cortex by Golgi staining and immunofluorescence. Results Foxp1-cKO mice had a deferred response to the tactile environment. However, the mice exhibited avoidance behavior and hyper-reaction following repeated whisker stimulation, similar to a fight-or-flight response. In contrast to the wild-type, c-Fos was activated in the basolateral amygdala but not in layer IV of the primary somatosensory cortex of the cKO mice. Moreover, Foxp1 deficiency in cortical neurons altered the dendrite development, reduced the number of dendritic spines, and disrupted barrel formation in the somatosensory cortex, suggesting impaired somatosensory processing may underlie the aberrant tactile responses. Limitations It is still unclear how the defective thalamocortical connection gives rise to the hyper-reactive response. Future experiments with electrophysiological recording are needed to analyze the role of thalamo-cortical-amygdala circuits in the disinhibiting amygdala and enhanced fearful responses in the mouse model of autism. Conclusions Foxp1-cKO mice have tactile sensory deficits while exhibit hyper-reactivity, which may represent fearful and emotional responses controlled by the amygdala. This study presents anatomical evidence for reduced thalamocortical connectivity in a genetic mouse model of ASD and demonstrates that the cerebral cortex can be the origin of atypical sensory behaviors. |
| first_indexed | 2024-03-10T17:43:05Z |
| format | Article |
| id | doaj.art-bb24050caec24a8492b05383d6475a83 |
| institution | Directory Open Access Journal |
| issn | 2040-2392 |
| language | English |
| last_indexed | 2024-03-10T17:43:05Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Autism |
| spelling | doaj.art-bb24050caec24a8492b05383d6475a832023-11-20T09:37:34ZengBMCMolecular Autism2040-23922023-09-0114111610.1186/s13229-023-00567-0Cortex-restricted deletion of Foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autismXue Li0Shishuai Hao1Shimin Zou2Xiaomeng Tu3Weixi Kong4Tian Jiang5Jie-Guang Chen6State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityState Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityState Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityState Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityState Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityResearch Center for Translational Medicine, The Affiliated Wenling Hospital of Wenzhou Medical UniversityState Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityAbstract Background Many children and young people with autism spectrum disorder (ASD) display touch defensiveness or avoidance (hypersensitivity), or engage in sensory seeking by touching people or objects (hyposensitivity). Abnormal sensory responses have also been noticed in mice lacking ASD-associated genes. Tactile sensory information is normally processed by the somatosensory system that travels along the thalamus to the primary somatosensory cortex. The neurobiology behind tactile sensory abnormalities, however, is not fully understood. Methods We employed cortex-specific Foxp1 knockout (Foxp1-cKO) mice as a model of autism in this study. Tactile sensory deficits were measured by the adhesive removal test. The mice’s behavior and neural activity were further evaluated by the whisker nuisance test and c-Fos immunofluorescence, respectively. We also studied the dendritic spines and barrel formation in the primary somatosensory cortex by Golgi staining and immunofluorescence. Results Foxp1-cKO mice had a deferred response to the tactile environment. However, the mice exhibited avoidance behavior and hyper-reaction following repeated whisker stimulation, similar to a fight-or-flight response. In contrast to the wild-type, c-Fos was activated in the basolateral amygdala but not in layer IV of the primary somatosensory cortex of the cKO mice. Moreover, Foxp1 deficiency in cortical neurons altered the dendrite development, reduced the number of dendritic spines, and disrupted barrel formation in the somatosensory cortex, suggesting impaired somatosensory processing may underlie the aberrant tactile responses. Limitations It is still unclear how the defective thalamocortical connection gives rise to the hyper-reactive response. Future experiments with electrophysiological recording are needed to analyze the role of thalamo-cortical-amygdala circuits in the disinhibiting amygdala and enhanced fearful responses in the mouse model of autism. Conclusions Foxp1-cKO mice have tactile sensory deficits while exhibit hyper-reactivity, which may represent fearful and emotional responses controlled by the amygdala. This study presents anatomical evidence for reduced thalamocortical connectivity in a genetic mouse model of ASD and demonstrates that the cerebral cortex can be the origin of atypical sensory behaviors.https://doi.org/10.1186/s13229-023-00567-0AutismTactileBarrel cortexThalamocorticalc-FosSpines |
| spellingShingle | Xue Li Shishuai Hao Shimin Zou Xiaomeng Tu Weixi Kong Tian Jiang Jie-Guang Chen Cortex-restricted deletion of Foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autism Molecular Autism Autism Tactile Barrel cortex Thalamocortical c-Fos Spines |
| title | Cortex-restricted deletion of Foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autism |
| title_full | Cortex-restricted deletion of Foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autism |
| title_fullStr | Cortex-restricted deletion of Foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autism |
| title_full_unstemmed | Cortex-restricted deletion of Foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autism |
| title_short | Cortex-restricted deletion of Foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autism |
| title_sort | cortex restricted deletion of foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autism |
| topic | Autism Tactile Barrel cortex Thalamocortical c-Fos Spines |
| url | https://doi.org/10.1186/s13229-023-00567-0 |
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