Journal
NEUROBIOLOGY OF LEARNING AND MEMORY
Volume 93, Issue 3, Pages 383-387Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nlm.2009.12.004
Keywords
GABA(A)R; Trace fear conditioning; Delay fear conditioning; alpha 4; delta; Tonic inhibition; Neurosteroids; Sex difference; Hippocampus
Funding
- NIH [AA13004, DE14184, GM47818, NS35985, AA07680]
- NINDS [P01NS35985]
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The GABA(A)R alpha 4 subunit is highly expressed in the dentate gyrus region of the hippocampus at predominantly extra synaptic locations where, along with the GABA(A)R delta 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 alpha 4 subunit-deficient mice using trace and delay fear conditioning, respectively. Mice were of a mixed C57B1/6J X 129S1/X1 genetic background from alpha 4 heterozygous breeding pairs. The alpha 4-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 delta knockout mice, but differences were present in both males and females. The convergent findings between alpha 4 and S knockout mice suggests that tonic inhibition mediated by alpha 4 beta delta GABA(A) receptors negatively modulates learning and memory processes and provides further evidence that tonic inhibition makes important functional contributions to learning and behavior. Published by Elsevier Inc.
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