title: The hippocampus plays a critical role at encoding discontiguous events for subsequent declarative memory expression in mice.
abstract: The hypothesis that hippocampal activity at encoding is causally related to subsequent declarative memory expression is tested in the mouse, by using lidocaine inactivation of the hippocampus in combination with c-fos neuroimaging analysis. We employed a two-stage radial maze paradigm of spatial discrimination, which was previously shown to dissociate between declarative and nondeclarative expression of memory related to the same acquired material. In Stage 1 (encoding), mice learnt the constant location of food among a set of six arms (three baited, three unbaited) by being submitted repeatedly to discontiguous experiences with each arm separately ("go/no-go" discrimination). In Stage 2 (test-session), they are challenged with novel presentations of the arms, which are either combined into pairs of opposite valence ("two-choice" discrimination), or opened all six together ("six-choice" discrimination). Previous experiments have demonstrated that the "two-choice" situation is a critical test for declarative memory while "six-choice" discrimination may rely on procedural memory. We observed that (i) hippocampal activity measured by c-fos mRNA expression was increased by "go/no-go" learning, and this activation was blocked by pre-training local infusions of lidocaine; (ii) when performed just before each session of Stage 1, such inactivation spared the acquisition of "go/no-go" discrimination but produced, subsequently, a selective deficit in the "two-choice" test (not in the "six-choice" test). This study indicates that the hippocampus is "spontaneously" engaged in encoding processes necessary for long-term storage of discontiguous experiences under a form enabling flexible declarative memory expression.
authors.affiliation: CNRS UMR 5106 Neurosciences Cognitives, Université Bordeaux 1 Avenue des Facultés, Talence, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Mingaud
authors.forename: Catherine
authors.initials: C
authors.lastname: Le Moine
authors.forename: Nicole
authors.initials: N
authors.lastname: Etchamendy
authors.forename: Cécile
authors.initials: C
authors.lastname: Mormède
authors.forename: Robert
authors.initials: R
authors.lastname: Jaffard
authors.forename: Aline
authors.initials: A
authors.lastname: Marighetto
mesh_terms: D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D017403:In Situ Hybridization; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology
chemical_list: D000779:Anesthetics, Local; D016760:Proto-Oncogene Proteins c-fos; D008012:Lidocaine