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    Autism-Associated Neuroligin-3 Mutations Commonly Impair Striatal Circuits to Boost Repetitive Behaviors

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    Issue Date
    2014-07-03
    Author
    Fuccillo, Marc V.
    Rothwell, Patrick E.
    Maxeiner, Stephan
    Hayton, Scott J.
    Gokce, Ozgun
    Lim, Byung Kook
    Fowler, Stephen C.
    Malenka, Robert C.
    Sudhof, Thomas C.
    Publisher
    Elsevier
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
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    Abstract
    In humans, neuroligin-3 mutations are associated with autism, while in mice the corresponding mutations produce robust synaptic and behavioral changes. However, different neuroligin-3 mutations cause largely distinct phenotypes in mice, and no causal relationship links a specific synaptic dysfunction to a behavioral change. Using rotarod motor learning as a proxy for acquired repetitive behaviors in mice, we found that different neuroligin-3 mutations uniformly enhanced formation of repetitive motor routines. Surprisingly, neuroligin-3 mutations caused this phenotype not via changes in the cerebellum or dorsal striatum, but via a selective synaptic impairment in the nucleus accumbens/ventral striatum. Here, neuroligin-3 mutations increased rotarod learning by specifically impeding synaptic inhibition onto D1-dopamine receptor-expressing but not D2-dopamine receptor-expressing medium spiny neurons. Our data thus suggest that different autism-associated neuroligin-3 mutations cause a common increase in acquired repetitive behaviors by impairing a specific striatal synapse, and thereby provide a plausible circuit substrate for autism pathophysiology.
    URI
    http://hdl.handle.net/1808/23205
    DOI
    https://doi.org/10.1016/j.cell.2014.04.045
    Collections
    • Pharmacy Scholarly Works [280]
    Citation
    Rothwell, Patrick E., Marc V. Fuccillo, Stephan Maxeiner, Scott J. Hayton, Ozgun Gokce, Byung Kook Lim, Stephen C. Fowler, Robert C. Malenka, and Thomas C. Sudhof. "Autism-Associated Neuroligin-3 Mutations Commonly Impair Striatal Circuits to Boost Repetitive Behaviors." Cell 158.1 (2014): 198-212.

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    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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