Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism.

TitleCerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism.
Publication TypeJournal Article
Year of Publication2014
AuthorsPiochon, C, Kloth, AD, Grasselli, G, Titley, HK, Nakayama, H, Hashimoto, K, Wan, V, Simmons, DH, Eissa, T, Nakatani, J, Cherskov, A, Miyazaki, T, Watanabe, M, Takumi, T, Kano, M, Wang, SS-H, Hansel, C
JournalNat Commun
Volume5
Pagination5586
Date Published2014 Nov 24
ISSN2041-1723
KeywordsAnimals, Autistic Disorder, Blinking, Cerebellum, Disease Models, Animal, DNA Copy Number Variations, Electrophysiology, Learning, Mice, Mice, Inbred C57BL, Mice, Transgenic, Motor Activity, Neuronal Plasticity, Patch-Clamp Techniques, Purkinje Cells, Synapses
Abstract

<p>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.</p>

DOI10.1038/ncomms6586
Alternate JournalNat Commun
PubMed ID25418414
PubMed Central IDPMC4243533
Grant ListUL1 TR000430 / TR / NCATS NIH HHS / United States
F31MH098651 / MH / NIMH NIH HHS / United States
F31 MH098651 / MH / NIMH NIH HHS / United States
NS045193 / NS / NINDS NIH HHS / United States
T32 MH020065 / MH / NIMH NIH HHS / United States
R01 NS045193 / NS / NINDS NIH HHS / United States