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LIMK, Cofilin 1 and actin dynamics involvement in fear memory processing.
Neurobiol Learn Mem. 2020 Jul 11; 173:107275.NL

Abstract

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.

Authors+Show Affiliations

Instituto de Fisiología, Biología Molecular y Neurociencias, Departamento de Fisiología, Biología Molecular y Celular, CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.Instituto de Fisiología, Biología Molecular y Neurociencias, Departamento de Fisiología, Biología Molecular y Celular, CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina. Electronic address: verodelaf@gmail.com.Max Planck Institute for Brain Research, 60438 Frankfurt, Germany.Max Planck Institute for Brain Research, 60438 Frankfurt, Germany.Max Planck Institute for Brain Research, 60438 Frankfurt, Germany.Max Planck Institute for Brain Research, 60438 Frankfurt, Germany.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.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.Max Planck Institute for Brain Research, 60438 Frankfurt, Germany.Max Planck Institute for Brain Research, 60438 Frankfurt, Germany.Instituto de Fisiología, Biología Molecular y Neurociencias, Departamento de Fisiología, Biología Molecular y Celular, CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina. Electronic address: aromano@fbmc.fcen.uba.ar.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32659348

Citation

Medina, Candela, et al. "LIMK, Cofilin 1 and Actin Dynamics Involvement in Fear Memory Processing." Neurobiology of Learning and Memory, vol. 173, 2020, p. 107275.
Medina C, de la Fuente V, Tom Dieck S, et al. LIMK, Cofilin 1 and actin dynamics involvement in fear memory processing. Neurobiol Learn Mem. 2020;173:107275.
Medina, C., de la Fuente, V., Tom Dieck, S., Nassim-Assir, B., Dalmay, T., Bartnik, I., Lunardi, P., de Oliveira Alvares, L., Schuman, E. M., Letzkus, J. J., & Romano, A. (2020). LIMK, Cofilin 1 and actin dynamics involvement in fear memory processing. Neurobiology of Learning and Memory, 173, 107275. https://doi.org/10.1016/j.nlm.2020.107275
Medina C, et al. LIMK, Cofilin 1 and Actin Dynamics Involvement in Fear Memory Processing. Neurobiol Learn Mem. 2020 Jul 11;173:107275. PubMed PMID: 32659348.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - LIMK, Cofilin 1 and actin dynamics involvement in fear memory processing. AU - Medina,Candela, AU - de la Fuente,Verónica, AU - Tom Dieck,Susanne, AU - Nassim-Assir,Belquis, AU - Dalmay,Tamas, AU - Bartnik,Ina, AU - Lunardi,Paula, AU - de Oliveira Alvares,Lucas, AU - Schuman,Erin M, AU - Letzkus,Johannes J, AU - Romano,Arturo, Y1 - 2020/07/11/ PY - 2019/12/09/received PY - 2020/05/29/revised PY - 2020/07/06/accepted PY - 2020/7/14/pubmed PY - 2020/7/14/medline PY - 2020/7/14/entrez KW - Cofilin KW - Consolidation KW - Extinction KW - Fear memory KW - LIMK KW - Reconsolidation SP - 107275 EP - 107275 JF - Neurobiology of learning and memory JO - Neurobiol Learn Mem VL - 173 N2 - 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. SN - 1095-9564 UR - https://www.unboundmedicine.com/medline/citation/32659348/LIMK,_Cofilin_1_and_actin_dynamics_involvement_in_fear_memory_processing L2 - https://linkinghub.elsevier.com/retrieve/pii/S1074-7427(20)30119-2 DB - PRIME DP - Unbound Medicine ER -
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