title: Critical role of the 65-kDa isoform of glutamic acid decarboxylase in consolidation and generalization of Pavlovian fear memory.
abstract: Evidence suggests that plasticity of the amygdalar and hippocampal GABAergic system is critical for fear memory formation. In this study we investigated in wild-type and genetically manipulated mice the role of the activity-dependent 65-kDa isozyme of glutamic acid decarboxylase (GAD65) in the consolidation and generalization of conditioned fear. First, we demonstrate a transient reduction of GAD65 gene expression in the dorsal hippocampus (6 h post training) and in the basolateral complex of the amygdala (24 h post training) during distinct phases of fear memory consolidation. Second, we show that targeted ablation of the GAD65 gene in Gad65(-/-) mice results in a pronounced context-independent, intramodal generalization of auditory fear memory during long-term (24 h or 14 d) but not short-term (30 min) memory retrieval. The temporal specificity of both gene regulation and memory deficits in Gad65 mutant mice suggests that GAD65-mediated GABA synthesis is critical for the consolidation of stimulus-specific fear memory. This function appears to involve a modulation of neural activity patterns in the amygdalo-hippocampal pathway as indicated by a reduction in theta frequency synchronization between the amygdala and hippocampus of Gad65(-/-) mice during the expression of generalized fear memory.
authors.affiliation: Institute for Physiology, Otto-von-Guericke University Magdeburg, D-39120 Magdeburg, Germany.
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Bergado-Acosta
authors.forename: Susan
authors.initials: S
authors.lastname: Sangha
authors.forename: Rajeevan T
authors.initials: RT
authors.lastname: Narayanan
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Obata
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Pape
authors.forename: Oliver
authors.initials: O
authors.lastname: Stork
mesh_terms: D000679:Amygdala / Q000201:enzymology; D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013216:Reflex, Startle / Q000502:physiology
chemical_list: D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2