Overproduction of Upper-Layer Neurons in the Neocortex Leads to Autism-like Features in Mice
| Autor: | Nancy Y. Ip, Amy K.Y. Fu, Weiwei Chen, Kai Liu, Wing-Ho Yung, Weiqun Fang, Liwen Jiang |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Dendritic Spines Population Neocortex Biology Inhibitory postsynaptic potential General Biochemistry Genetics and Molecular Biology Mice Neurodevelopmental disorder Interneurons mental disorders medicine Animals Autistic Disorder education lcsh:QH301-705.5 Cell Proliferation Progenitor education.field_of_study Anatomy medicine.disease Phenotype medicine.anatomical_structure lcsh:Biology (General) nervous system Synapses Excitatory postsynaptic potential Autism Neuroscience |
| Zdroj: | Cell Reports, Vol 9, Iss 5, Pp 1635-1643 (2014) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2014.11.003 |
| Popis: | Summary: The functional integrity of the neocortex depends upon proper numbers of excitatory and inhibitory neurons; however, the consequences of dysregulated neuronal production during the development of the neocortex are unclear. As excess cortical neurons are linked to the neurodevelopmental disorder autism, we investigated whether the overproduction of neurons leads to neocortical malformation and malfunction in mice. We experimentally increased the number of pyramidal neurons in the upper neocortical layers by using the small molecule XAV939 to expand the intermediate progenitor population. The resultant overpopulation of neurons perturbs development of dendrites and spines of excitatory neurons and alters the laminar distribution of interneurons. Furthermore, these phenotypic changes are accompanied by dysregulated excitatory and inhibitory synaptic connection and balance. Importantly, these mice exhibit behavioral abnormalities resembling those of human autism. Thus, our findings collectively suggest a causal relationship between neuronal overproduction and autism-like features, providing developmental insights into the etiology of autism. : Fang et al. generated a mouse model with excessive excitatory neurons in the neocortex by manipulating embryonic neurogenesis. Overproduction of neurons results in autism-like anatomical and behavioral features. These findings suggest a causal relationship between overproduction of neurons and cortical malfunction and provide developmental insights into the etiology of autism. |
| Databáze: | OpenAIRE |
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