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Inhibition of protein synthesis or mTOR in the basolateral amygdala blocks retrieval-induced memory strengthening

  • Translational Neurosciences - Original Article
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Abstract

Fear memory retrieval can lead to either reconsolidation (accompanied or not by strengthening of the memory trace) or extinction. Here, we show that non-reinforced retrieval of inhibitory avoidance (IA) conditioning can induce memory strengthening assessed in a subsequent retention test trial. Infusion of the protein synthesis inhibitor cycloheximide or the mTOR inhibitor rapamycin into the rat basolateral complex of the amygdala (BLA) after a reactivation (retrieval) session impaired retrieval-induced strengthening. Intra-BLA infusion of the mRNA synthesis inhibitor 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB) after retrieval had no effect. These findings provide the first evidence suggesting that non-reinforced IA retrieval can lead to memory strengthening through a mechanism dependent on protein synthesis and mTOR activity in the BLA.

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References

  • Alberini CM (2005) Mechanisms of memory stabilization: are consolidation and reconsolidation similar or distinct processes? Trends Neurosci 28:51–56

    Article  PubMed  CAS  Google Scholar 

  • Alberini CM (2009) Transcription factors in long-term memory and synaptic plasticity. Physiol Rev 89:121–145

    Article  PubMed  CAS  Google Scholar 

  • Alberini CM (2011) The role of reconsolidation and the dynamic process of long-term memory formation and storage. Front Behav Neurosci 5:12

    Article  PubMed  Google Scholar 

  • Amaral OB, Osan R, Roesler R, Tort AB (2008) A synaptic reinforcement-based model for transient amnesia following disruptions of memory consolidation and reconsolidation. Hippocampus 18:584–601

    Article  PubMed  Google Scholar 

  • Blundell J, Kouser M, Powell CM (2008) Systemic inhibition of mammalian target of rapamycin inhibits fear memory reconsolidation. Neurobiol Learn Mem 90:28–35

    Article  PubMed  CAS  Google Scholar 

  • Chuang JY, Lin KY, Cherng CG, Yu L (2012) Involvement of amygdaloid protein synthesis in early- and late-phase reconsolidation of emotion-related memories. Chin J Physiol 55:314–322

    PubMed  CAS  Google Scholar 

  • Comim CM, Constantino LS, Petronilho F, Quevedo J, Dal-Pizzol F (2011) Aversive memory in sepsis survivor rats. J Neural Transm 118:213–237

    Article  PubMed  Google Scholar 

  • Costa-Mattioli M, Sossin WS, Klann E, Sonenberg N (2009) Translational control of long-lasting synaptic plasticity and memory. Neuron 61:10–26

    Article  PubMed  CAS  Google Scholar 

  • Dudai Y, Eisenberg M (2004) Rites of passage of the engram: reconsolidation and the lingering consolidation hypothesis. Neuron 44:93–100

    Article  PubMed  CAS  Google Scholar 

  • Duvarci S, Nader K, LeDoux JE (2005) Activation of extracellular signal-regulated kinase- mitogen-activated protein kinase cascade in the amygdala is required for memory reconsolidation of auditory fear conditioning. Eur J Neurosci 21:283–289

    Article  PubMed  Google Scholar 

  • Duvarci S, Nader K, LeDoux JE (2008) De novo mRNA synthesis is required for both consolidation and reconsolidation of fear memories in the amygdala. Learn Mem 15:747–755

    Article  PubMed  Google Scholar 

  • Eisenberg M, Kobilo T, Berman DE, Dudai Y (2003) Stability of retrieved memory: inverse correlation with trace dominance. Science 301:1102–1104

    Article  PubMed  CAS  Google Scholar 

  • Hay N, Sonenberg N (2004) Upstream and downstream of mTOR. Genes Dev 18:1926–1945

    Article  PubMed  CAS  Google Scholar 

  • Hoeffer CA, Klann E (2010) mTOR signaling: at the crossroads of plasticity, memory and disease. Trends Neurosci 33:67–75

    Article  PubMed  CAS  Google Scholar 

  • Inda MC, Muravieva EV, Alberini CM (2011) Memory retrieval and the passage of time: from reconsolidation and strengthening to extinction. J Neurosci 31:1635–1643

    Article  PubMed  CAS  Google Scholar 

  • Jobim PF, Pedroso TR, Christoff RR, Werenicz A, Maurmann N, Reolon GK, Roesler R (2012a) Inhibition of mTOR by rapamycin in the amygdala or hippocampus impairs formation and reconsolidation of inhibitory avoidance memory. Neurobiol Learn Mem 97:105–112

    Article  PubMed  CAS  Google Scholar 

  • Jobim PF, Pedroso TR, Werenicz A, Christoff RR, Maurmann N, Reolon GK, Schröder N, Roesler R (2012b) Impairment of object recognition memory by rapamycin inhibition of mTOR in the amygdala or hippocampus around the time of learning or reactivation. Behav Brain Res 228:151–158

    Article  PubMed  CAS  Google Scholar 

  • Lee JL (2008) Memory reconsolidation mediates the strengthening of memories by additional learning. Nat Neurosci 11:1264–1266

    Article  PubMed  CAS  Google Scholar 

  • Lee JL, Milton AL, Everitt BJ (2006) Reconsolidation and extinction of conditioned fear: inhibition and potentiation. J Neurosci 26:10051–10056

    Article  PubMed  CAS  Google Scholar 

  • Luft T, Flores DG, Vianna MR, Schwartsmann G, Roesler R, Izquierdo I (2006) A role for hippocampal gastrin-releasing peptide receptors in extinction of aversive memory. NeuroReport 17:935–939

    Article  PubMed  CAS  Google Scholar 

  • Luft T, Amaral OB, Schwartsmann G, Roesler R (2008) Transient disruption of fear-related memory by post-retrieval inactivation of gastrin-releasing peptide or N-methyl-D-aspartate receptors in the hippocampus. Curr Neurovasc Res 5:21–27

    Article  PubMed  CAS  Google Scholar 

  • McGaugh JL (2000) Memory: a century of consolidation. Science 287:248–251

    Article  PubMed  CAS  Google Scholar 

  • McGaugh JL (2002) Memory consolidation and the amygdala: a systems perspective. Trends Neurosci 25:456–461

    Article  PubMed  CAS  Google Scholar 

  • Milekic MH, Alberini CM (2002) Temporally graded requirement for protein synthesis following memory reactivation. Neuron 36:521–525

    Article  PubMed  CAS  Google Scholar 

  • Milekic MH, Pollonini G, Alberini CM (2007) Temporal requirement of C/EBPbeta in the amygdala following reactivation but not acquisition of inhibitory avoidance. Learn Mem 14:504–511

    Article  PubMed  CAS  Google Scholar 

  • Nader K, Schafe GE, Le Doux JE (2000) Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406:722–726

    Article  PubMed  CAS  Google Scholar 

  • Parsons RG, Gafford GM, Baruch DE, Riedner BA, Helmstetter FJ (2006a) Long-term stability of fear memory depends on the synthesis of protein but not mRNA in the amygdala. Eur J Neurosci 23:1853–1859

    Article  PubMed  Google Scholar 

  • Parsons RG, Gafford GM, Helmstetter FJ (2006b) Translational control via the mammalian target of rapamycin (mTOR) pathway is critical for the formation and stability of long term fear memory in amygdala neurons. J Neurosci 26:12977–12983

    Article  PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (2007) The Rat Brain in Stereotaxic Coordinates, 6th edn. Academic Press, San Diego

  • Pedreira ME, Maldonado H (2003) Protein synthesis subserves reconsolidation or extinction depending on reminder duration. Neuron 38:863–869

    Article  PubMed  CAS  Google Scholar 

  • Quevedo J, Vianna MR, Roesler R, de-Paris F, Izquierdo I, Rose SP (1999) Two time windows of anisomycin-induced amnesia for inhibitory avoidance training in rats: protection from amnesia by pretraining but not pre-exposure to the task apparatus. Learn Mem 6:600–607

    Article  PubMed  CAS  Google Scholar 

  • Quevedo J, Vianna MR, Roesler R, Martins MR, de-Paris F, Medina JH, Izquierdo I (2005) Pretraining but not preexposure to the task apparatus prevents the memory impairment induced by blockade of protein synthesis, PKA or MAP kinase in rats. Neurochem Res 30:61–67

    Article  PubMed  CAS  Google Scholar 

  • Rao-Ruiz P, Rotaru DC, van der Loo RJ, Mansvelder HD, Stiedl O, Smit AB, Spijker S (2011) Retrieval-specific endocytosis of GluA2-AMPARs underlies adaptive reconsolidation of contextual fear. Nat Neurosci 14:1302–1308

    Article  PubMed  CAS  Google Scholar 

  • Roesler R, McGaugh JL (2010) Memory Consolidation. In: Koob GF, Le Moal M, Thompson RF (eds) Encyclopedia of Behavioral Neuroscience, vol 2. Academic Press, Oxford, pp 206–214

    Chapter  Google Scholar 

  • Roesler R, Quevedo J (2009) Retrieval mediated by hippocampal extracellular signal-regulated kinase/mitogen-activated protein kinase is required for memory strengthening. Neuroscience 160:711–715

    Article  PubMed  CAS  Google Scholar 

  • Roesler R, Vianna M, Sant’Anna MK, Kuyven CR, Kruel AV, Quevedo J, Ferreira MB (1998) Intrahippocampal infusion of the NMDA receptor antagonist AP5 impairs retention of an inhibitory avoidance task: protection from impairment by pretraining or preexposure to the task apparatus. Neurobiol Learn Mem 69:87–91

    Article  PubMed  CAS  Google Scholar 

  • Roesler R, Vianna MR, de-Paris F, Rodrigues C, Sant’Anna MK, Quevedo J, Ferreira MB (2000) NMDA receptor antagonism in the basolateral amygdala blocks enhancement of inhibitory avoidance learning in previously trained rats. Behav Brain Res 112:99–105

    Article  PubMed  CAS  Google Scholar 

  • Sara SJ (2000a) Retrieval and reconsolidation: toward a neurobiology of remembering. Learn Mem 7:73–84

    Article  PubMed  CAS  Google Scholar 

  • Sara SJ (2000b) Strengthening the shaky trace through retrieval. Nat Rev Neurosci 1:212–213

    Article  PubMed  CAS  Google Scholar 

  • Suzuki A, Josselyn SA, Frankland PW, Masushige S, Silva AJ, Kida S (2004) Memory reconsolidation and extinction have distinct temporal and biochemical signatures. J Neurosci 24:4787–4795

    Article  PubMed  CAS  Google Scholar 

  • Vianna MR, Szapiro G, McGaugh JL, Medina JH, Izquierdo I (2001) Retrieval of memory for fear-motivated training initiates extinction requiring protein synthesis in the rat hippocampus. Proc Natl Acad Sci USA 98:12251–12254

    Article  PubMed  CAS  Google Scholar 

  • Vianna MR, Igaz LM, Coitinho AS, Medina JH, Izquierdo I (2003) Memory extinction requires gene expression in rat hippocampus. Neurobiol Learn Mem 79:199–203

    Article  PubMed  CAS  Google Scholar 

  • Vianna MR, Coitinho AS, Izquierdo I (2004) Role of the hippocampus and amygdala in the extinction of fear-motivated learning. Curr Neurovasc Res 1:55–60

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by the National Council for Scientific and Technological Development (CNPq; grants 303703/2009-1 and 484185/2012-8 to R.R.), the National Institute for Translational Medicine (INCT-TM), and the HCPA institutional research fund (FIPE/HCPA). T.R.P is supported by fellowships from the Coordination for the Improvement of Higher Education Personnel (CAPES).

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Authors and Affiliations

  1. Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 (ICBS, Campus Centro/UFRGS), Porto Alegre, RS, 90050-170, Brazil

    Thiago R. Pedroso, Paulo F. C. Jobim, Leonardo M. Carvalho, Raissa R. Christoff, Natasha Maurmann, Gustavo K. Reolon, Aline Werenicz & Rafael Roesler

  2. Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, 90035-003, Brazil

    Thiago R. Pedroso, Paulo F. C. Jobim, Leonardo M. Carvalho, Raissa R. Christoff, Natasha Maurmann, Gustavo K. Reolon, Aline Werenicz & Rafael Roesler

  3. National Institute for Translational Medicine (INCT-TM), Porto Alegre, Brazil

    Thiago R. Pedroso, Paulo F. C. Jobim, Leonardo M. Carvalho, Raissa R. Christoff, Natasha Maurmann, Gustavo K. Reolon, Aline Werenicz & Rafael Roesler

Authors
  1. Thiago R. Pedroso
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  2. Paulo F. C. Jobim
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  3. Leonardo M. Carvalho
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  4. Raissa R. Christoff
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  5. Natasha Maurmann
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  6. Gustavo K. Reolon
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  7. Aline Werenicz
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  8. Rafael Roesler
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Correspondence to Rafael Roesler.

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Pedroso, T.R., Jobim, P.F.C., Carvalho, L.M. et al. Inhibition of protein synthesis or mTOR in the basolateral amygdala blocks retrieval-induced memory strengthening. J Neural Transm 120, 1525–1531 (2013). https://doi.org/10.1007/s00702-013-1032-y

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  • DOI: https://doi.org/10.1007/s00702-013-1032-y

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