title: Effects of Hippocampal LIMK Inhibition on Memory Acquisition, Consolidation, Retrieval, Reconsolidation, and Extinction.
abstract: Long-lasting changes in dendritic spines provide a physical correlate for memory formation and persistence. LIM kinase (LIMK) plays a critical role in orchestrating dendritic actin dynamics during memory processing, since it is the convergent downstream target of both the Rac1/PAK and RhoA/ROCK pathways that in turn induce cofilin phosphorylation and prevent depolymerization of actin filaments. Here, using a potent LIMK inhibitor (BMS-5), we investigated the role of LIMK activity in the dorsal hippocampus during contextual fear memory in rats. We first found that post-training administration of BMS-5 impaired memory consolidation in a dose-dependent manner. Inhibiting LIMK before training also disrupted memory acquisition. We then demonstrated that hippocampal LIMK activity seems to be critical for memory retrieval and reconsolidation, since both processes were impaired by BMS-5 treatment. Contextual fear memory extinction, however, was not sensitive to the same treatment. In conclusion, our findings demonstrate that hippocampal LIMK activity plays an important role in memory acquisition, consolidation, retrieval, and reconsolidation during contextual fear conditioning.
authors.affiliation: Laboratório de Neurobiologia da Memória, Departamento de Biofísica, Instituto de Biociências, Universidade Federal do Rio Grande do Sul (UFRGS), Avenida Bento Gonçalves, 9500, Prédio 43422, Sala 216A, Porto Alegre, Rio Grande do Sul, 91501-970, Brazil.|Graduate Program in Neuroscience, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Paula
authors.initials: P
authors.lastname: Lunardi
authors.affiliation: Laboratório de Neurobiologia da Memória, Departamento de Biofísica, Instituto de Biociências, Universidade Federal do Rio Grande do Sul (UFRGS), Avenida Bento Gonçalves, 9500, Prédio 43422, Sala 216A, Porto Alegre, Rio Grande do Sul, 91501-970, Brazil.|Graduate Program in Neuroscience, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Ricardo Marcelo
authors.initials: RM
authors.lastname: Sachser
authors.affiliation: Psychobiology and Neurocomputation Lab, Biophysics Department, Bioscience Institute, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.|Graduate Program in Neuroscience, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Rodrigo Ordoñez
authors.initials: RO
authors.lastname: Sierra
authors.affiliation: Laboratório de Neurobiologia da Memória, Departamento de Biofísica, Instituto de Biociências, Universidade Federal do Rio Grande do Sul (UFRGS), Avenida Bento Gonçalves, 9500, Prédio 43422, Sala 216A, Porto Alegre, Rio Grande do Sul, 91501-970, Brazil.|Graduate Program in Neuroscience, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Lizeth Katherine
authors.initials: LK
authors.lastname: Pedraza
authors.affiliation: Laboratorio de Neurobiología de la Memoria, Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Candela
authors.initials: C
authors.lastname: Medina
authors.affiliation: Laboratorio de Neurobiología de la Memoria, Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Verónica
authors.initials: V
authors.lastname: de la Fuente
authors.affiliation: Laboratorio de Neurobiología de la Memoria, Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Arturo
authors.initials: A
authors.lastname: Romano
authors.affiliation: Psychobiology and Neurocomputation Lab, Biophysics Department, Bioscience Institute, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.|Graduate Program in Neuroscience, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Jorge Alberto
authors.initials: JA
authors.lastname: Quillfeldt
authors.affiliation: Laboratório de Neurobiologia da Memória, Departamento de Biofísica, Instituto de Biociências, Universidade Federal do Rio Grande do Sul (UFRGS), Avenida Bento Gonçalves, 9500, Prédio 43422, Sala 216A, Porto Alegre, Rio Grande do Sul, 91501-970, Brazil. lucas.alvares@ufrgs.br.|Graduate Program in Neuroscience, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. lucas.alvares@ufrgs.br.
authors.forename: Lucas
authors.initials: L
authors.lastname: de Oliveira Alvares
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D054461:Lim Kinases / Q000037:antagonists & inhibitors*; D008297:Male; D008568:Memory / Q000187:drug effects*; D000069077:Memory Consolidation / Q000187:drug effects*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D054461:Lim Kinases
keywords: BMS-5; Dorsal hippocampus; Memory; Rats