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

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

Author information

1
Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany.
2
Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria.
3
Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany.
4
Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany. Electronic address: rhee@em.mpg.de.
5
Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany. Electronic address: brose@em.mpg.de.

Abstract

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.

PMID:
26456829
PMCID:
PMC5862414
DOI:
10.1016/j.celrep.2015.09.011
[Indexed for MEDLINE]
Free PMC Article

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