dc.contributor.author | Fuccillo, Marc V. | |
dc.contributor.author | Rothwell, Patrick E. | |
dc.contributor.author | Maxeiner, Stephan | |
dc.contributor.author | Hayton, Scott J. | |
dc.contributor.author | Gokce, Ozgun | |
dc.contributor.author | Lim, Byung Kook | |
dc.contributor.author | Fowler, Stephen C. | |
dc.contributor.author | Malenka, Robert C. | |
dc.contributor.author | Sudhof, Thomas C. | |
dc.date.accessioned | 2017-02-20T22:05:25Z | |
dc.date.available | 2017-02-20T22:05:25Z | |
dc.date.issued | 2014-07-03 | |
dc.identifier.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. | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23205 | |
dc.description.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. | en_US |
dc.publisher | Elsevier | en_US |
dc.subject | Autism | en_US |
dc.subject | Synaptic transmission | en_US |
dc.subject | Synaptic plasticity | en_US |
dc.subject | Stereotypic behaviors | en_US |
dc.subject | Motor learning | en_US |
dc.subject | Striatum | en_US |
dc.subject | N. accumbens | en_US |
dc.subject | Neuroligin | en_US |
dc.subject | Synaptic cell adhesion | en_US |
dc.subject | Neurexin | en_US |
dc.title | Autism-Associated Neuroligin-3 Mutations Commonly Impair Striatal Circuits to Boost Repetitive Behaviors | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Fowler, Stephen C. | |
kusw.kudepartment | Pharmacology & Toxicology | en_US |
dc.identifier.doi | 10.1016/j.cell.2014.04.045 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess | |