期刊
JOURNAL OF NEUROSCIENCE
卷 36, 期 48, 页码 12129-12143出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1849-16.2016
关键词
autism; cerebellum; excitatory synapse; GluD2; Purkinje cell; Shank2
资金
- National Research Foundation (NRF) [NRF-2013H1A2A1032785 250]
- NRF-Fostering Core Leaders of the Future Basic 249 Science Program
- MSIP Grant [2008-0062282]
- Korea Institute of Science and Technology Institutional Program [2E26190]
- Institute for Basic Science [IBS-R002-D1]
- Ministry of Science, ICT & Future Planning, Republic of Korea [2E26190] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2013H1A2A1032785] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Shank2 is a multidomain scaffolding protein implicated in the structural and functional coordination of multiprotein complexes at excitatory postsynaptic sites as well as in psychiatric disorders, including autism spectrum disorders. While Shank2 is strongly expressed in the cerebellum, whether Shank2 regulates cerebellar excitatory synapses, or contributes to the behavioral abnormalities observed in Shank2(-/-) mice, remains unexplored. Here we show that Shank2(-/-) mice show reduced excitatory synapse density in cerebellar Purkinje cells in association with reduced levels of excitatory postsynaptic proteins, including GluD2 and PSD-93, and impaired motor coordination in the Erasmus test. Shank2 deletion restricted to Purkinje cells (Pcp2-Cre; Shank2(fl/fl) mice) leads to similar reductions in excitatory synapse density, synaptic protein levels, and motor coordination. Pcp2-Cre; Shank2(fl/fl) mice do not recapitulate autistic-like behaviors observed in Shank2(-/-) mice, such as social interaction deficits, altered ultrasonic vocalizations, repetitive behaviors, and hyperactivity. However, Pcp2-Cre; Shank2(fl/fl) mice display enhanced repetitive behavior in the hole-board test and anxiety-like behavior in the light-dark test, which are not observed in Shan2(-/-) mice. These results implicate Shank2 in the regulation of cerebellar excitatory synapse density, motor coordination, and specific repetitive and anxiety-like behaviors.
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