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Neurodevelopmental Disorders

開催日 2014/9/13
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Enhanced remodeling of specific synapses in mouse models of autism

  • P3-320
  • 田中 慎二 / Shinji Tanaka:1 一色 真明 / Masaaki Isshiki:1 栗生 俊彦 / Toshihiko Kuriu:2 田渕 克彦 / Katsuhiko Tabuchi:3 内匠 透 / Toru Takumi:4 岡部 繁男 / Shigeo Okabe:1 
  • 1:東京大院・医・神経細胞生物 / Dept Cell Neurobiol, Univ of Tokyo, Tokyo, Japan 2:徳島文理大・香川薬・薬理 / Dept Neurophysiol, Kagawa Sch of Pharmaceutical Sci, Kagawa, Japan 3:信州大院・医・分子細胞生理 / Dept of Mol Cell Physiol, Shinshu Univ Sch of Med, Nagano, Japan 4:理研BSI・精神生物学 / Lab for Mental Biol, RIKEN BSI, Saitama, Japan 

Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental conditions characterized by impairments of social behaviors. Developmental deficits in neural connectivity are hypothesized as an underlying mechanism of ASDs. By using the technique of in vivo two-photon microscopy, we have reported that spine turnover was increased in two distinct ASD model mice which mimicked the human 15q11-13 duplication and neuroligin-3 R451C point mutation. To test whether enhanced turnover was restricted in specific spines, we classified spines by the presence of exogenously expressed GFP-tagged gephyrin, a scaffolding protein of inhibitory synapses. Immunohistochemical analysis revealed that gephyrin-positive and -negative spines colocalized with VGluT2 and VGluT1 immunoreactive puncta, respectively. This indicated that gephyrin could be a good marker for discriminating the spines receiving the inputs from thalamic and intracortical neurons. In vivo imaging of wild-type mice over 2 days revealed that gephyrin-positive spines were larger and highly stable. In both ASD mouse models, enhanced turnover was seen only in the fraction of gephyrin-negative spines, and gephyrin-positive spines were very stable similarly to wilid-type mice. To test whether activity-dependent regulation of neural activity is disturbed in ASD mouse models, we performed immunostaining of c-fos after the stimulation of specific row of whiskers. The density of c-fos immunoreactive cells in the layer 2/3 was decreased in both ASD mouse models. These results suggest that spines receiving intracortical projections are specifically affected in the developing cortex of ASD mouse models. This selective impairment may affect integration of information in the cortex and underlie ASD symptoms.

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