Perturbed Hippocampal Synaptic Inhibition and γ-Oscillations in a Neuroligin-4 Knockout Mouse Model of Autism

Cell Rep. 2015 Oct 20;13(3):516-523. doi: 10.1016/j.celrep.2015.09.011. Epub 2015 Oct 8.


Loss-of-function mutations in the synaptic adhesion protein Neuroligin-4 are among the most common genetic abnormalities associated with autism spectrum disorders, but little is known about the function of Neuroligin-4 and the consequences of its loss. We assessed synaptic and network characteristics in Neuroligin-4 knockout mice, focusing on the hippocampus as a model brain region with a critical role in cognition and memory, and found that Neuroligin-4 deletion causes subtle defects of the protein composition and function of GABAergic synapses in the hippocampal CA3 region. Interestingly, these subtle synaptic changes are accompanied by pronounced perturbations of γ-oscillatory network activity, which has been implicated in cognitive function and is altered in multiple psychiatric and neurodevelopmental disorders. Our data provide important insights into the mechanisms by which Neuroligin-4-dependent GABAergic synapses may contribute to autism phenotypes and indicate new strategies for therapeutic approaches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autistic Disorder / genetics*
  • CA3 Region, Hippocampal / cytology
  • CA3 Region, Hippocampal / growth & development
  • CA3 Region, Hippocampal / metabolism*
  • Cell Adhesion Molecules, Neuronal / genetics*
  • GABAergic Neurons / metabolism
  • GABAergic Neurons / physiology
  • Gamma Rhythm*
  • Inhibitory Postsynaptic Potentials*
  • Male
  • Mice
  • Mice, Inbred C57BL


  • Cell Adhesion Molecules, Neuronal
  • Nlgn4 protein, mouse