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

Cell reports 2015 Oct 20

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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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Matthieu Hammer, Dilja Krueger-Burg, Liam Patrick Tuffy, Benjamin Hillman Cooper, Holger Taschenberger, Sarit Pati Goswami, Hannelore Ehrenreich, Peter Jonas, Frederique Varoqueaux, Jeong-Seop Rhee, Nils Brose. Perturbed Hippocampal Synaptic Inhibition and γ-Oscillations in a Neuroligin-4 Knockout Mouse Model of Autism. Cell reports. 2015 Oct 20;13(3):516-523