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

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 path...

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Bibliographic Details
Published in:Molecular neurobiology 2018-02, Vol.55 (2), p.958-967
Main Authors: Lunardi, Paula, Sachser, Ricardo Marcelo, Sierra, Rodrigo Ordoñez, Pedraza, Lizeth Katherine, Medina, Candela, de la Fuente, Verónica, Romano, Arturo, Quillfeldt, Jorge Alberto, de Oliveira Alvares, Lucas
Format: Article
Language:English
Subjects:
Actin
Animals
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cofilin
Conditioning (Psychology) - drug effects
Dendritic spines
Depolymerization
Enzyme Inhibitors - pharmacology
Extinction behavior
Extinction, Psychological - drug effects
Fear - drug effects
Fear conditioning
Filaments
Hippocampus
Hippocampus - drug effects
LIM kinase
Lim Kinases - antagonists & inhibitors
Male
Memory
Memory - drug effects
Memory Consolidation - drug effects
Neurobiology
Neurology
Neurosciences
Pain Threshold - drug effects
Phosphorylation
Rac1 protein
Rats
Rats, Wistar
Rho-associated kinase
RhoA protein
Rodents
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Summary: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.
ISSN:0893-7648
1559-1182
DOI:10.1007/s12035-016-0361-x