GABAA receptors containing the α5 subunit mediate the trace effect in aversive and appetitive conditioning and extinction of conditioned fear

被引:102
作者
Yee, BK
Hauser, J
Dolgov, VV
Keist, R
Möhler, H
Rudolph, U
Feldon, J
机构
[1] Swiss Fed Inst Technol, Lab Behav Neurobiol, CH-8603 Schwerzenbach, Switzerland
[2] Univ Zurich, Inst Pharmacol & Toxicol, CH-8057 Zurich, Switzerland
[3] Swiss Fed Inst Technol, Dept Chem & Appl Biosci, CH-8057 Zurich, Switzerland
关键词
extinction; GABA; hippocampus; learning; memory; trace conditioning;
D O I
10.1111/j.1460-9568.2004.03642.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
A reduction in alpha5 subunit-containing gamma-aminobutyric acid (GABA)(A) receptors has been reported to enhance some forms of learning in mutant mouse models. This effect has been attributed to impaired alpha5 GABA(A) receptor-mediated inhibitory modulation in the hippocampus. The introduction of a point mutation (H105R) in the alpha5 subunit is associated with a specific reduction of alpha5 subunit-containing GABA(A) receptors in the hippocampus. The present study examined the modulation of associative learning and the extinction of conditioned response in these animals. The strength of classical conditioning can be weakened when a trace interval is interposed between the conditioned stimulus and unconditioned stimulus. Here we report that this 'trace effect' in classical conditioning was absent in the mutant mice - they were insensitive to the imposition of a 20-s trace interval. This effect of the mutation was most clearly in the female mice using an aversive conditioning paradigm, and in the male mice using an appetitive conditioning paradigm. These gender-specific phenotypes were accompanied by a resistance to extinction of conditioned fear response in the mutant mice that was apparent in both genders. Our results identify neuronal inhibition in the hippocampus mediated via alpha5 GABA(A) receptors as a critical control element in the regulation of the acquisition and expression of associative memory.
引用
收藏
页码:1928 / 1936
页数:9
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