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.

Resilience and Vulnerability to Trauma: Early Life Interventions Modulate Aversive Memory Reconsolidation in the Dorsal Hippocampus

“…A significant reactivation-induced increase in β-actin was also found for all neonatal treatments ( F (1,30) = 8.354, p = 0.007, 2w-ANOVA, main effect of Reactivation; Figures 5G–H); this effect is in accordance with previous reports that show that actin filaments proliferation is necessary for reconsolidation (Rehberg et al, 2010; Lamprecht, 2016; Lunardi et al, 2018; Popik et al, 2018). No significant interaction ( F (2,30) = 1.178, p = 0.322, 2w-ANOVA) or main effect of neonatal intervention ( F (2,30) = 0.274, p = 0.762, 2w-ANOVA) were found.…”

A time‐dependent contribution of hippocampal CB1, CB2 and PPARγ receptors to cannabidiol‐induced disruption of fear memory consolidation

“…Classically, the memory consolidation time‐window lasts 6 hr (McGaugh, 2000), a period in which cellular and molecular events occur to stabilize and store a newly acquired long‐term memory (Lamprecht & LeDoux, 2004; McGaugh, 2000). Most studies investigating the effects of pharmacological interventions on memory consolidation are conducted at very short intervals after the acquisition, that is, 0–10 min (Lunardi et al, 2017; Schmidt et al, 2017). Few have explored longer intervals of the consolidation time‐window.…”

Activation of Rac1 Has an Opposing Effect on Induction and Maintenance of Long-Term Potentiation in Hippocampus by Acting on Different Kinases

“…We further studied how Rac1 activation results in a decrease in the expression of PKMζ. We examined the influence of a specific LIMK inhibitor BMS-5 (Lunardi et al, 2018 ) on Rac1-induced decrease in the expression of PKMζ. The rats were divided into three groups:a control group where ACSF was applied, CN04 group where CN04 was applied, and CN04 + BMS-5 group where CN04 and BMS-5 were co-applied.…”