Rothwell_2014_Cell_158_198

Reference

Title : Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors - Rothwell_2014_Cell_158_198
Author(s) : Rothwell PE , Fuccillo MV , Maxeiner S , Hayton SJ , Gokce O , Lim BK , Fowler SC , Malenka RC , Sudhof TC
Ref : Cell , 158 :198 , 2014
Abstract :

In humans, neuroligin-3 mutations are associated with autism, whereas 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. PAPERFLICK:

PubMedSearch : Rothwell_2014_Cell_158_198
PubMedID: 24995986

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Citations formats

Rothwell PE, Fuccillo MV, Maxeiner S, Hayton SJ, Gokce O, Lim BK, Fowler SC, Malenka RC, Sudhof TC (2014)
Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors
Cell 158 :198

Rothwell PE, Fuccillo MV, Maxeiner S, Hayton SJ, Gokce O, Lim BK, Fowler SC, Malenka RC, Sudhof TC (2014)
Cell 158 :198