Cortex-restricted deletion of Foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autism

Molecular Autism

Research

Tian Jiang¹  Xue Li²  Shishuai Hao²  Xiaomeng Tu²  Weixi Kong²  Jie-Guang Chen²  Shimin Zou² 

[1] Research Center for Translational Medicine, The Affiliated Wenling Hospital of Wenzhou Medical University, 317500, Wenling, People’s Republic of China;State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, 325027, Wenzhou, Zhejiang, People’s Republic of China;School of Biomedical Engineering, Wenzhou Medical University, 325027, Wenzhou, People’s Republic of China;

关键词: Autism;    Tactile;    Barrel cortex;    Thalamocortical;    c-Fos;    Spines;   

DOI  :  10.1186/s13229-023-00567-0

 received in 2023-04-12, accepted in 2023-09-05,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMany 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.MethodsWe 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.ResultsFoxp1-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.LimitationsIt 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.ConclusionsFoxp1-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.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

12888_2023_5168_Article_IEq3.gif

12888_2023_5172_Article_IEq15.gif

Fig. 4

12888_2023_5145_Article_IEq1.gif

Fig. 1

Fig. 1

41534_2023_763_Article_IEq2.gif

40708_2023_201_Article_IEq6.gif