LIMK, Cofilin 1 and actin dynamics involvement in fear memory processing

• Published in: Neurobiology of learning and memory 2020-09, Vol.173, p.107275-107275, Article 107275
• Main Authors: Medina, Candela, de la Fuente, Verónica, tom Dieck, Susanne, Nassim-Assir, Belquis, Dalmay, Tamas, Bartnik, Ina, Lunardi, Paula, de Oliveira Alvares, Lucas, Schuman, Erin M., Letzkus, Johannes J., Romano, Arturo
• Format: Article
• Language: English
• Subjects: Cofilin; Consolidation; Extinction; Fear memory; LIMK; Reconsolidation
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2020.107275

•LIMK inhibition impairs memory reconsolidation, as well as memory consolidation.•Cfl1 activity is inhibited and its mRNA downregulated in CA1 neuropil after memory reactivation.•Actb mRNA is upregulated in CA1 somata after memory reactivation.•Fear memory extinction is bidirectionally affected by modulation of actin dynamics. Long-term memory has been associated with morphological changes in the brain, which in turn tightly correlate with changes in synaptic efficacy. Such plasticity is proposed to rely on dendritic spines as a neuronal canvas on which these changes can occur. Given the key role of actin cytoskeleton dynamics in spine morphology, major regulating factors of this process such as Cofilin 1 (Cfl1) and LIM kinase (LIMK), an inhibitor of Cfl1 activity, are prime molecular targets that may regulate dendritic plasticity. Using a contextual fear conditioning paradigm in mice, we found that pharmacological induction of depolymerization of actin filaments through the inhibition of LIMK causes an impairment in memory reconsolidation, as well as in memory consolidation. On top of that, Cfl1 activity is inhibited and its mRNA is downregulated in CA1 neuropil after re-exposure to the training context. Moreover, by pharmacological disruption of actin cytoskeleton dynamics, the process of memory extinction can either be facilitated or impaired. Our results lead to a better understanding of the role of LIMK, Cfl1 and actin cytoskeleton dynamics in the morphological and functional changes underlying the synaptic plasticity of the memory trace.