Cerebellar associative sensory learning defects in five mouse autism models
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- Alexander D Kloth
- Department of Molecular Biology and Princeton Neuroscience Institute, Princeton University, Princeton, United States
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- Aleksandra Badura
- Department of Molecular Biology and Princeton Neuroscience Institute, Princeton University, Princeton, United States
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- Amy Li
- Department of Molecular Biology and Princeton Neuroscience Institute, Princeton University, Princeton, United States
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- Adriana Cherskov
- Department of Molecular Biology and Princeton Neuroscience Institute, Princeton University, Princeton, United States
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- Sara G Connolly
- Department of Molecular Biology and Princeton Neuroscience Institute, Princeton University, Princeton, United States
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- Andrea Giovannucci
- Department of Molecular Biology and Princeton Neuroscience Institute, Princeton University, Princeton, United States
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- M Ali Bangash
- Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
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- Giorgio Grasselli
- Department of Neurobiology, University of Chicago, Chicago, United States
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- Olga Peñagarikano
- Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
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- Claire Piochon
- Department of Neurobiology, University of Chicago, Chicago, United States
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- Peter T Tsai
- The F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital Boston, Harvard Medical School, Boston, United States
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- Daniel H Geschwind
- Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
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- Christian Hansel
- Department of Neurobiology, University of Chicago, Chicago, United States
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- Mustafa Sahin
- The F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital Boston, Harvard Medical School, Boston, United States
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- Toru Takumi
- RIKEN Brain Science Institute, Wako, Japan
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- Paul F Worley
- Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
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- Samuel S-H Wang
- Department of Molecular Biology and Princeton Neuroscience Institute, Princeton University, Princeton, United States
説明
<jats:p>Sensory integration difficulties have been reported in autism, but their underlying brain-circuit mechanisms are underexplored. Using five autism-related mouse models, Shank3+/ΔC, Mecp2R308/Y, Cntnap2−/−, L7-Tsc1 (L7/Pcp2Cre::Tsc1flox/+), and patDp(15q11-13)/+, we report specific perturbations in delay eyeblink conditioning, a form of associative sensory learning requiring cerebellar plasticity. By distinguishing perturbations in the probability and characteristics of learned responses, we found that probability was reduced in Cntnap2−/−, patDp(15q11-13)/+, and L7/Pcp2Cre::Tsc1flox/+, which are associated with Purkinje-cell/deep-nuclear gene expression, along with Shank3+/ΔC. Amplitudes were smaller in L7/Pcp2Cre::Tsc1flox/+ as well as Shank3+/ΔC and Mecp2R308/Y, which are associated with granule cell pathway expression. Shank3+/ΔC and Mecp2R308/Y also showed aberrant response timing and reduced Purkinje-cell dendritic spine density. Overall, our observations are potentially accounted for by defects in instructed learning in the olivocerebellar loop and response representation in the granule cell pathway. Our findings indicate that defects in associative temporal binding of sensory events are widespread in autism mouse models.</jats:p>
収録刊行物
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- eLife
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eLife 4 e06085-, 2015-07-09
eLife Sciences Publications, Ltd
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詳細情報 詳細情報について
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- CRID
- 1360848665469515008
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- ISSN
- 2050084X
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
