Trace and contextual fear conditioning is enhanced in mice lacking the α4 subunit of the GABAA receptor

• Published in: Neurobiology of learning and memory Vol. 93; no. 3; pp. 383 - 387
• Main Authors: MOORE, M. D, CUSHMAN, J, CHANDRA, D, HOMANICS, G. E, OLSEN, R. W, FANSELOW, M. S
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 01-03-2010
• Subjects: Behavioral psychophysiology; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Affect affectivity; Neurosteroids; Central nervous system; Sex; Neurosteroid; Subunit; Encephalon; Tonic inhibition; Learning; R; Acquisition process; Inhibition; α4; Rodentia; Emotion emotionality; Classical conditioning; Sex difference; Fear; Vertebrata; Mammalia; Mouse; δ; Animal; GABA; Delay fear conditioning; Trace fear conditioning; Gabaergic receptor A; Hippocampus
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2009.12.004

The GABA
A
R α4 subunit is highly expressed in the dentate gyrus region of the hippocampus at predominantly extra-synaptic locations where, along with the GABA
A
R δ subunit, it forms GABA
A
receptors that mediate a tonic inhibitory current. The present study was designed to test hippocampus-dependent and hippocampus-independent learning and memory in GABA
A
R α4 subunit-deficient mice using trace and delay fear conditioning, respectively. Mice were of a mixed C57Bl/6J X 129S1/X1 genetic background from α4 heterozygous breeding pairs. The α4-knockout mice showed enhanced trace and contextual fear conditioning consistent with an enhancement of hippocampus-dependent learning and memory. These enhancements were sex-dependent, similar to previous studies in GABA
A
R δ knockout mice, but differences were present in both males and females. The convergent findings between α4 and δ-knockout mice suggests that tonic inhibition mediated by α4βδ GABA
A
receptors negatively modulates learning and memory processes and provides further evidence that tonic inhibition makes important functional contributions to learning and behavior.