2. Academic Validation
  3. Effects of Hippocampal LIMK Inhibition on Memory Acquisition, Consolidation, Retrieval, Reconsolidation, and Extinction

Effects of Hippocampal LIMK Inhibition on Memory Acquisition, Consolidation, Retrieval, Reconsolidation, and Extinction

  • Mol Neurobiol. 2018 Feb;55(2):958-967. doi: 10.1007/s12035-016-0361-x.
Paula Lunardi 1 2,  Ricardo Marcelo Sachser 1 2,  Rodrigo Ordoñez Sierra 3 2,  Lizeth Katherine Pedraza 1 2,  Candela Medina 4,  Verónica de la Fuente 4,  Arturo Romano 4,  Jorge Alberto Quillfeldt 3 2,  Lucas de Oliveira Alvares 5 6
Affiliations

Affiliations

  • 1 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.
  • 2 Graduate Program in Neuroscience, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
  • 3 Psychobiology and Neurocomputation Lab, Biophysics Department, Bioscience Institute, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
  • 4 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.
  • 5 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.
  • 6 Graduate Program in Neuroscience, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. lucas.alvares@ufrgs.br.
PMID: 28084590 DOI: 10.1007/s12035-016-0361-x
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.

Keywords

BMS-5; Dorsal hippocampus; Memory; Rats.

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