title: Inhibition of c-Jun N-terminal kinase in the CA1 region of the dorsal hippocampus blocks extinction of inhibitory avoidance memory.
abstract: Step-down inhibitory avoidance (IA) memory formation involves association of stepping-down from a platform present in a training box (conditioned stimulus) with a footshock (unconditioned stimulus). A single short training session is enough to induce a lasting and strong memory trace expressed as an increase in step-down latency. Repeated nonreinforced retrieval, however, induces extinction of the IA response, a process involving a new learning that overrules the original one to indicate that the conditioned stimulus no longer predicts the unconditioned stimulus. Although the molecular requirements of IA memory consolidation are well understood, comparatively less is known about the signaling pathways involved in its extinction. Here we report that, when given into dorsal CA1 immediately but not 180 min after daily nonreinforced retrieval sessions, SP60015, a specific inhibitor of the mitogen-activated protein kinase, c-Jun N-terminal kinase, impaired IA memory extinction in a dose-dependent manner without producing any motor or perceptual impairment or damaging the hippocampal formation. Our results suggest that, as happens during consolidation, extinction of IA long-term memory also requires c-Jun N-terminal kinase activity in the CA1 region of the dorsal hippocampus.
authors.affiliation: Center for Memory Research, Biomedical Research Institute, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Lia R M
authors.initials: LR
authors.lastname: Bevilaqua
authors.forename: Janine I
authors.initials: JI
authors.lastname: Rossato
authors.forename: Julia H R
authors.initials: JH
authors.lastname: Clarke
authors.forename: Jorge H
authors.initials: JH
authors.lastname: Medina
authors.forename: Iván
authors.initials: I
authors.lastname: Izquierdo
authors.forename: Martín
authors.initials: M
authors.lastname: Cammarota
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000008:administration & dosage / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000528:radiation effects; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D015398:Signal Transduction
chemical_list: D000873:Anthracenes; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases