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Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism
by
Miyazaki, Taisuke
, Wan, Vivian
, Wang, Samuel S.-H.
, Grasselli, Giorgio
, Kano, Masanobu
, Watanabe, Masahiko
, Eissa, Tahra
, Cherskov, Adriana
, Piochon, Claire
, Hansel, Christian
, Hashimoto, Kouichi
, Simmons, Dana H.
, Nakayama, Hisako
, Titley, Heather K.
, Nakatani, Jin
, Takumi, Toru
, Kloth, Alexander D.
in
631/378/1595
/ 631/378/1689/1373
/ 631/378/2632/1368
/ Animals
/ Autistic Disorder - physiopathology
/ Blinking - physiology
/ Cerebellum - physiology
/ Deregulation
/ Disease Models, Animal
/ DNA Copy Number Variations - genetics
/ Electrophysiology
/ Fibers
/ Humanities and Social Sciences
/ Learning - physiology
/ Mice
/ Mice, Inbred C57BL
/ Mice, Transgenic
/ Motor Activity - genetics
/ Motor Activity - physiology
/ multidisciplinary
/ Neuronal Plasticity - genetics
/ Neuronal Plasticity - physiology
/ Patch-Clamp Techniques
/ Plasticity
/ Purkinje Cells - physiology
/ Science
/ Science (multidisciplinary)
/ Social behavior
/ Synapses - physiology
2014
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Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism
by
Miyazaki, Taisuke
, Wan, Vivian
, Wang, Samuel S.-H.
, Grasselli, Giorgio
, Kano, Masanobu
, Watanabe, Masahiko
, Eissa, Tahra
, Cherskov, Adriana
, Piochon, Claire
, Hansel, Christian
, Hashimoto, Kouichi
, Simmons, Dana H.
, Nakayama, Hisako
, Titley, Heather K.
, Nakatani, Jin
, Takumi, Toru
, Kloth, Alexander D.
in
631/378/1595
/ 631/378/1689/1373
/ 631/378/2632/1368
/ Animals
/ Autistic Disorder - physiopathology
/ Blinking - physiology
/ Cerebellum - physiology
/ Deregulation
/ Disease Models, Animal
/ DNA Copy Number Variations - genetics
/ Electrophysiology
/ Fibers
/ Humanities and Social Sciences
/ Learning - physiology
/ Mice
/ Mice, Inbred C57BL
/ Mice, Transgenic
/ Motor Activity - genetics
/ Motor Activity - physiology
/ multidisciplinary
/ Neuronal Plasticity - genetics
/ Neuronal Plasticity - physiology
/ Patch-Clamp Techniques
/ Plasticity
/ Purkinje Cells - physiology
/ Science
/ Science (multidisciplinary)
/ Social behavior
/ Synapses - physiology
2014
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Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism
by
Miyazaki, Taisuke
, Wan, Vivian
, Wang, Samuel S.-H.
, Grasselli, Giorgio
, Kano, Masanobu
, Watanabe, Masahiko
, Eissa, Tahra
, Cherskov, Adriana
, Piochon, Claire
, Hansel, Christian
, Hashimoto, Kouichi
, Simmons, Dana H.
, Nakayama, Hisako
, Titley, Heather K.
, Nakatani, Jin
, Takumi, Toru
, Kloth, Alexander D.
in
631/378/1595
/ 631/378/1689/1373
/ 631/378/2632/1368
/ Animals
/ Autistic Disorder - physiopathology
/ Blinking - physiology
/ Cerebellum - physiology
/ Deregulation
/ Disease Models, Animal
/ DNA Copy Number Variations - genetics
/ Electrophysiology
/ Fibers
/ Humanities and Social Sciences
/ Learning - physiology
/ Mice
/ Mice, Inbred C57BL
/ Mice, Transgenic
/ Motor Activity - genetics
/ Motor Activity - physiology
/ multidisciplinary
/ Neuronal Plasticity - genetics
/ Neuronal Plasticity - physiology
/ Patch-Clamp Techniques
/ Plasticity
/ Purkinje Cells - physiology
/ Science
/ Science (multidisciplinary)
/ Social behavior
/ Synapses - physiology
2014
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Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism
Journal Article
Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism
2014
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Overview
A common feature of autism spectrum disorder (ASD) is the impairment of motor control and learning, occurring in a majority of children with autism, consistent with perturbation in cerebellar function. Here we report alterations in motor behaviour and cerebellar synaptic plasticity in a mouse model (patDp/+) for the human 15q11-13 duplication, one of the most frequently observed genetic aberrations in autism. These mice show ASD-resembling social behaviour deficits. We find that in patDp/+ mice delay eyeblink conditioning—a form of cerebellum-dependent motor learning—is impaired, and observe deregulation of a putative cellular mechanism for motor learning, long-term depression (LTD) at parallel fibre-Purkinje cell synapses. Moreover, developmental elimination of surplus climbing fibres—a model for activity-dependent synaptic pruning—is impaired. These findings point to deficits in synaptic plasticity and pruning as potential causes for motor problems and abnormal circuit development in autism.
Impairments of cerebellar-dependent motor control and learning are implicated in some forms of autism spectrum disorder (ASD). In this study, the authors provide a characterization of the motor deficits and cerebellar function abnormalities in a transgenic mouse model of ASD.
Publisher
Nature Publishing Group UK,Nature Publishing Group
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