NDLI: Trace fear conditioning involves hippocampal alpha5 GABA(A) receptors.

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Trace fear conditioning involves hippocampal alpha5 GABA(A) receptors.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Benke, D. Crestani, F. Keist, R. Prut, L. Blüthmann, H. Fritschy, J-m Möhler, H. Vogt, K. Rudolph, U.
Description	Author Affiliation: Crestani F ( Institute of Pharmacology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.);
Abstract	The heterogeneity of gamma-aminobutyric acid type A (GABA(A)) receptors contributes to the diversity of neuronal inhibition in the regulation of information processing. Although most GABA(A) receptors are located synaptically, the small population of alpha5GABA(A) receptors is largely expressed extrasynaptically. To clarify the role of the alpha5GABA(A) receptors in the control of behavior, a histidine-to-arginine point mutation was introduced in position 105 of the murine alpha5 subunit gene, which rendered the alpha5GABA(A) receptors diazepam-insensitive. Apart from an incomplete muscle relaxing effect, neither the sedative, anticonvulsant, nor anxiolytic-like activity of diazepam was impaired in alpha5(H105R) mice. However, in hippocampal pyramidal cells, the point mutation resulted in a selective reduction of alpha5GABA(A) receptors, which altered the drug-independent behavior. In line with the role of the hippocampus in certain forms of associative learning, trace fear conditioning, but not delay conditioning or contextual conditioning, was facilitated in the mutant mice. Trace fear conditioning differs from delay conditioning in that the conditioned and unconditioned stimulus are separated by a time interval. Thus, the largely extrasynaptic alpha5GABA(A) receptors in hippocampal pyramidal cells are implicated as control elements of the temporal association of threat cues in trace fear conditioning.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	13
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Conditioning, Classical Hippocampus Physiology Receptors, GABA-A Animals Behavior, Animal Immunohistochemistry In Vitro Techniques Long-Term Potentiation Mice Point Mutation Drug Effects Genetics Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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