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

• Main Authors: 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
• Format: Article
• Language: English
• Published: Elsevier 2015-10-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124715010220

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.