期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：13
页码：8980-8985
DOI：10.1073/pnas.142288699
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The heterogeneity of {gamma}-aminobutyric acid type A (GABAA) receptors contributes to the diversity of neuronal inhibition in the regulation of information processing. Although most GABAA receptors are located synaptically, the small population of 5GABAA receptors is largely expressed extrasynaptically. To clarify the role of the 5GABAA receptors in the control of behavior, a histidine-to-arginine point mutation was introduced in position 105 of the murine 5 subunit gene, which rendered the 5GABAA receptors diazepam-insensitive. Apart from an incomplete muscle relaxing effect, neither the sedative, anticonvulsant, nor anxiolytic-like activity of diazepam was impaired in 5(H105R) mice. However, in hippocampal pyramidal cells, the point mutation resulted in a selective reduction of 5GABAA 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 5GABAA receptors in hippocampal pyramidal cells are implicated as control elements of the temporal association of threat cues in trace fear conditioning.
