title: Perturbed Hippocampal Synaptic Inhibition and γ-Oscillations in a Neuroligin-4 Knockout Mouse Model of Autism.
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.
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Hammer
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany.
authors.forename: Dilja
authors.initials: D
authors.lastname: Krueger-Burg
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany.
authors.forename: Liam Patrick
authors.initials: LP
authors.lastname: Tuffy
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany.
authors.forename: Benjamin Hillman
authors.initials: BH
authors.lastname: Cooper
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Taschenberger
authors.affiliation: Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria.
authors.forename: Sarit Pati
authors.initials: SP
authors.lastname: Goswami
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Ehrenreich
authors.affiliation: Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Jonas
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany.
authors.forename: Frederique
authors.initials: F
authors.lastname: Varoqueaux
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany. Electronic address: rhee@em.mpg.de.
authors.forename: Jeong-Seop
authors.initials: JS
authors.lastname: Rhee
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Göttingen, Germany. Electronic address: brose@em.mpg.de.
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics*; D056654:CA3 Region, Hippocampal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D059330:GABAergic Neurons / Q000378:metabolism / Q000502:physiology; D065818:Gamma Rhythm; D053444:Inhibitory Postsynaptic Potentials; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C527118:Nlgn4 protein, mouse