A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice

Katsuhiko Tabuchi, Jacqueline Blundell, Mark R. Etherton, Robert E Hammer, Xinran Liu, Craig M Powell, Thomas C. Südhof

Research output: Contribution to journalArticle

609 Scopus citations

Abstract

Autism spectrum disorders (ASDs) are characterized by impairments in social behaviors that are sometimes coupled to specialized cognitive abilities. A small percentage of ASD patients carry mutations in genes encoding neuroligins, which are postsynaptic cell-adhesion molecules. We introduced one of these mutations into mice: the Arg451→Cys451 (R451C) substitution in neuroligin-3. R451C mutant mice showed impaired social interactions but enhanced spatial learning abilities. Unexpectedly, these behavioral changes were accompanied by an increase in inhibitory synaptic transmission with no apparent effect on excitatory synapses. Deletion of neuroligin-3, in contrast, did not cause such changes, indicating that the R451C substitution represents a gain-of-function mutation. These data suggest that increased inhibitory synaptic transmission may contribute to human ASDs and that the R451C knockin mice may be a useful model for studying autism-related behaviors.

Original languageEnglish (US)
Pages (from-to)71-76
Number of pages6
JournalScience
Volume318
Issue number5847
DOIs
StatePublished - Oct 5 2007

    Fingerprint

ASJC Scopus subject areas

  • General

Cite this

Tabuchi, K., Blundell, J., Etherton, M. R., Hammer, R. E., Liu, X., Powell, C. M., & Südhof, T. C. (2007). A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science, 318(5847), 71-76. https://doi.org/10.1126/science.1146221