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Genetically altered AMPA-type glutamate receptor kinetics in interneurons disrupt long-range synchrony of gamma oscillation

Fuchs, F.C., Doheny, H., Faulkner, H., Caputi, A., Traub, R.D., Bibbig, A., Kopell, N., Whittington, M.A. and Monyher, H. (2001) Genetically altered AMPA-type glutamate receptor kinetics in interneurons disrupt long-range synchrony of gamma oscillation. Proceedings of the National Academy of Sciences, 98 (6). pp. 3571-3576. ISSN 0027-8424

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Gamma oscillations synchronized between distant neuronal populations may be critical for binding together brain regions devoted to common processing tasks. Network modeling predicts that such synchrony depends in part on the fast time course of excitatory postsynaptic potentials (EPSPs) in interneurons, and that even moderate slowing of this time course will disrupt synchrony. We generated mice with slowed interneuron EPSPs by gene targeting, in which the gene encoding the 67-kDa form of glutamic acid decarboxylase (GAD67) was altered to drive expression of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor subunit GluR-B. GluR-B is a determinant of the relatively slow EPSPs in excitatory neurons and is normally expressed at low levels in γ-aminobutyric acid (GABA)ergic interneurons, but at high levels in the GAD-GluR-B mice. In both wild-type and GAD-GluR-B mice, tetanic stimuli evoked gamma oscillations that were indistinguishable in local field potential recordings. Remarkably, however, oscillation synchrony between spatially separated sites was severely disrupted in the mutant, in association with changes in interneuron firing patterns. The congruence between mouse and model suggests that the rapid time course of AMPA receptor-mediated EPSPs in interneurons might serve to allow gamma oscillations to synchronize over distance.

Item Type: Article
Copyright, Publisher and Additional Information: Copyright © 2001 by the National Academy of Sciences
Institution: The University of Leeds
Academic Units: The University of Leeds > Faculty of Biological Sciences (Leeds) > Institute of Membrane and Systems Biology (Leeds)
Depositing User: Sherpa Assistant
Date Deposited: 14 Mar 2006
Last Modified: 07 Jun 2014 00:07
Published Version: http://www.pnas.org/cgi/content/full/98/6/3571
Status: Published
Refereed: Yes
Identification Number: 10.1073/pnas.051631898
URI: http://eprints.whiterose.ac.uk/id/eprint/566

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