Trace Fear Conditioning Is Enhanced in Mice Lacking the [delta] Subunit of the GABA[subscript [Alpha]] Receptor

Autor/inn/en	Wiltgen, Brian J.; Sanders, Matthew J.; Ferguson, Carolyn; Homanics, Gregg E.; Fanselow, Michael S.
Titel	Trace Fear Conditioning Is Enhanced in Mice Lacking the [delta] Subunit of the GABA[subscript [Alpha]] Receptor
Quelle	In: Learning & Memory, 12 (2005) 3, S.327-333 (7 Seiten) PDF als Volltext Verfügbarkeit
Sprache	englisch
Dokumenttyp	gedruckt; online; Zeitschriftenaufsatz
ISSN	1072-0502
DOI	10.1101/lm.89705
Schlagwörter	Conditioning; Inhibition; Fear; Animals; Learning Processes; Molecular Structure; Brain; Neurological Organization; Comparative Analysis; Gender Differences; Memory + Suchen Sie Ihr Suchwort? Hemmung; Furcht; Animal; Tier; Tiere; Learning process; Lernprozess; Gehirn; Geschlechterkonflikt; Gedächtnis
Abstract	The [delta] subunit of the GABA[subscript [Alpha]] receptor (GABA[subscript [Alpha]]R) is highly expressed in the dentate gyrus of the hippocampus. Genetic deletion of this subunit reduces synaptic and extrasynaptic inhibition and decreases sensitivity to neurosteroids. This paper examines the effect of these changes on hippocampus-dependent trace fear conditioning. Compared to controls, knockout mice exhibited enhanced acquisition of tone and context fear. Hippocampus-independent delay conditioning was normal in these animals. These results suggest that reduced inhibition in the dentate gyrus facilitates the acquisition of trace fear conditioning. However, the enhancement in trace conditioning was only observed in female knockout mice. The sex-specificity of this effect may be a result of neuroactive steroids. These compounds vary during the estrus cycle, can increase GABAergic inhibition, and have been shown to impair hippocampus-dependent learning. We propose that activation of GABA[subscript [Alpha]]Rs by neuroactive steroids inhibits learning processes in the hippocampus. Knockouts are immune to this effect because of the reduced neurosteroid sensitivity that accompanies deletion of the [delta] subunit. Relationships between neurosteroids, hippocampal excitability, and memory are discussed. (Contains 4 figures.) (Author).
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Erfasst von	ERIC (Education Resources Information Center), Washington, DC
Update	2017/4/10