1. Perturbed Hippocampal Synaptic Inhibition and γ-Oscillations in a Neuroligin-4 Knockout Mouse Model of Autism.
- Author
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Hammer M, Krueger-Burg D, Tuffy LP, Cooper BH, Taschenberger H, Goswami SP, Ehrenreich H, Jonas P, Varoqueaux F, Rhee JS, and Brose N
- Subjects
- Animals, CA3 Region, Hippocampal cytology, CA3 Region, Hippocampal growth & development, GABAergic Neurons metabolism, GABAergic Neurons physiology, Male, Mice, Mice, Inbred C57BL, Autistic Disorder genetics, CA3 Region, Hippocampal metabolism, Cell Adhesion Molecules, Neuronal genetics, Gamma Rhythm, Inhibitory Postsynaptic Potentials
- 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., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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