title: Calcineurin inhibition blocks within-, but not between-session fear extinction in mice.
abstract: Memory extinction involves the formation of a new associative memory that inhibits a previously conditioned association. Nonetheless, it could also depend on weakening of the original memory trace if extinction is assumed to have multiple components. The phosphatase calcineurin (CaN) has been described as being involved in extinction but not in the initial consolidation of fear learning. With this in mind, we set to study whether CaN could have different roles in distinct components of extinction. Systemic treatment with the CaN inhibitors cyclosporin A (CsA) or FK-506, as well as i.c.v. administration of CsA, blocked within-session, but not between-session extinction or initial learning of contextual fear conditioning. Similar effects were found in multiple-session extinction of contextual fear conditioning and in auditory fear conditioning, indicating that CaN is involved in different types of short-term extinction. Meanwhile, inhibition of protein synthesis by cycloheximide (CHX) treatment did not affect within-session extinction, but disrupted fear acquisition and slightly impaired between-session extinction. Our results point to a dissociation of within- and between-session extinction of fear conditioning, with the former being more dependent on CaN activity and the latter on protein synthesis. Moreover, the modulation of within-session extinction did not affect between-session extinction, suggesting that these components are at least partially independent.
authors.affiliation: Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, RJ, 22290-290, Brazil suellen_almeida@psych.mpg.de.
authors.forename: Suellen
authors.initials: S
authors.lastname: Almeida-Corrêa
authors.affiliation: Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, RJ, 22290-290, Brazil.
authors.forename: Thiago C
authors.initials: TC
authors.lastname: Moulin
authors.affiliation: Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, RJ, 22290-290, Brazil.
authors.forename: Clarissa F D
authors.initials: CF
authors.lastname: Carneiro
authors.affiliation: Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, RJ, 22290-290, Brazil.
authors.forename: Marina M C
authors.initials: MM
authors.lastname: Gonçalves
authors.affiliation: Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, RJ, 22290-290, Brazil.
authors.forename: Lara S
authors.initials: LS
authors.lastname: Junqueira
authors.affiliation: Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, RJ, 22290-290, Brazil.
authors.forename: Olavo B
authors.initials: OB
authors.lastname: Amaral
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000494:pharmacology / Q000502:physiology*; D065095:Calcineurin Inhibitors / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D016572:Cyclosporine / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D057967:Infusions, Intraventricular; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D065095:Calcineurin Inhibitors; D016572:Cyclosporine; D019703:Calcineurin; D016559:Tacrolimus