Journal of Molecular Neuroscience

, Volume 65, Issue 2, pp 127–140 | Cite as

Transcriptional Regulation Involved in Fear Memory Reconsolidation

  • Xu Wang
  • Min Li
  • Haitao Zhu
  • Yongju Yu
  • Yuanyuan Xu
  • Wenmo Zhang
  • Chen BianEmail author


Memory reconsolidation has been demonstrated to offer a potential target period during which the fear memories underlying fear disorders can be disrupted. Reconsolidation is a labile stage that consolidated memories re-enter after memories are reactivated. Reactivated memories, induced by cues related to traumatic events, are susceptible to strengthening and weakening. Gene transcription regulation and protein synthesis have been suggested to be required for fear memory reconsolidation. Investigating the transcriptional regulation mechanisms underlying reconsolidation may provide a therapeutic method for the treatment of fear disorders such as post-traumatic stress disorder (PTSD). However, the therapeutic effect of treating a fear disorder through interfering with reconsolidation is still contradictory. In this review, we summarize several transcription factors that have been linked to fear memory reconsolidation and propose that transcription factors, as well as related signaling pathways can serve as targets for fear memory interventions. Then, we discuss the application of pharmacological and behavioral interventions during reconsolidation that may or not efficiently treat fear disorders.


Fear memory Reconsolidation Transcriptional factor Post-traumatic stress disorder 



This work was supported by the National Science Foundation of China (NSFC, No. 31500896) and Natural Science Foundation Project of CQ (cstc2016jcyjA0587).

Compliance with ethical standards

Conflicts of Interest

The authors declare that they have no conflicts of interest.


  1. Abel T, Lattal KM (2001) Molecular mechanisms of memory acquisition, consolidation and retrieval. Curr Opin Neurobiol 11:180–187PubMedCrossRefGoogle Scholar
  2. Adachi M, Lin PY, Pranav H, Monteggia LM (2016) Postnatal loss of Mef2c results in dissociation of effects on synapse number and learning and memory. Biol Psychiatry 80:140–148PubMedCrossRefGoogle Scholar
  3. Akhtar MW, Kim MS, Adachi M, Morris MJ, Qi X, Richardson JA, Bassel-Duby R, Olson EN, Kavalali ET, Monteggia LM (2012) In vivo analysis of MEF2 transcription factors in synapse regulation and neuronal survival. PLoS One 7:e34863PubMedPubMedCentralCrossRefGoogle Scholar
  4. Alberini CM (2005) Mechanisms of memory stabilization: are consolidation and reconsolidation similar or distinct processes? Trends Neurosci 28:51–56PubMedCrossRefGoogle Scholar
  5. Alberini CM (2009) Transcription factors in long-term memory and synaptic plasticity. Physiol Rev 89:121–145PubMedCrossRefGoogle Scholar
  6. Alberini CM, Ledoux JE (2013) Memory reconsolidation. Curr Biol 23:R746–R750PubMedCrossRefGoogle Scholar
  7. Anest V, Hanson JL, Cogswell PC, Steinbrecher KA, Strahl BD, Baldwin AS (2003) A nucleosomal function for IkappaB kinase-alpha in NF-kappaB-dependent gene expression. Nature 423:659–663PubMedCrossRefGoogle Scholar
  8. Arikkath J, Reichardt LF (2008) Cadherins and catenins at synapses: roles in synaptogenesis and synaptic plasticity. Trends Neurosci 31:487–494PubMedPubMedCentralCrossRefGoogle Scholar
  9. Auber A, Tedesco V, Jones CE, Monfils MH, Chiamulera C (2013) Post-retrieval extinction as reconsolidation interference: methodological issues or boundary conditions? Psychopharmacology 226:631–647PubMedPubMedCentralCrossRefGoogle Scholar
  10. Baldi E, Bucherelli C (2015) Brain sites involved in fear memory reconsolidation and extinction of rodents. Neurosci Biobehav Rev 53:160–190PubMedCrossRefGoogle Scholar
  11. Bamji SX, Rico B, Kimes N, Reichardt LF (2006) BDNF mobilizes synaptic vesicles and enhances synapse formation by disrupting cadherin-beta-catenin interactions. J Cell Biol 174:289–299PubMedPubMedCentralCrossRefGoogle Scholar
  12. Barbosa AC, Kim MS, Ertunc M, Adachi M, Nelson ED, McAnally J, Richardson JA, Kavalali ET, Monteggia LM, Bassel-Duby R, Olson EN (2008) MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function. Proc Natl Acad Sci U S A 105:9391–9396PubMedPubMedCentralCrossRefGoogle Scholar
  13. Barnes P, Kirtley A, Thomas KL (2012) Quantitatively and qualitatively different cellular processes are engaged in CA1 during the consolidation and reconsolidation of contextual fear memory. Hippocampus 22:149–171PubMedCrossRefGoogle Scholar
  14. Besnard A, Caboche J, Laroche S (2013) Recall and reconsolidation of contextual fear memory: differential control by ERK and Zif268 expression dosage. PLoS One 8:e72006PubMedPubMedCentralCrossRefGoogle Scholar
  15. Besnard A, Laroche S, Caboche J (2014) Comparative dynamics of MAPK/ERK signalling components and immediate early genes in the hippocampus and amygdala following contextual fear conditioning and retrieval. Brain Struct Funct 219:415–430PubMedCrossRefGoogle Scholar
  16. Boccia M, Freudenthal R, Blake M, de la Fuente V, Acosta G, Baratti C, Romano A (2007) Activation of hippocampal nuclear factor-kappa B by retrieval is required for memory reconsolidation. J Neurosci 27:13436–13445PubMedCrossRefGoogle Scholar
  17. Boersma MC, Meffert MK (2008) Novel roles for the NF-kappaB signaling pathway in regulating neuronal function. Sci Signal 1:pe7PubMedCrossRefGoogle Scholar
  18. Bozon B, Davis S, Laroche S (2003) A requirement for the immediate early gene zif268 in reconsolidation of recognition memory after retrieval. Neuron 40:695–701PubMedCrossRefGoogle Scholar
  19. Brunet A, Orr SP, Tremblay J, Robertson K, Nader K, Pitman RK (2008) Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder. J Psychiatr Res 42:503–506PubMedCrossRefGoogle Scholar
  20. Cadigan KM, Waterman ML (2012) TCF/LEFs and Wnt signaling in the nucleus. Cold Spring Harb Perspect Biol 4Google Scholar
  21. Chan WY, Leung HT, Westbrook RF, McNally GP (2010) Effects of recent exposure to a conditioned stimulus on extinction of Pavlovian fear conditioning. Learn Mem 17:512–521PubMedPubMedCentralCrossRefGoogle Scholar
  22. Charney DS, Woods SW, Krystal JH, Nagy LM, Heninger GR (1992) Noradrenergic neuronal dysregulation in panic disorder: the effects of intravenous yohimbine and clonidine in panic disorder patients. Acta Psychiatr Scand 86:273–282PubMedCrossRefGoogle Scholar
  23. Chia C, Otto T (2013) Hippocampal Arc (Arg3.1) expression is induced by memory recall and required for memory reconsolidation in trace fear conditioning. Neurobiol Learn Mem 106:48–55PubMedCrossRefGoogle Scholar
  24. Chou D, Huang CC, Hsu KS (2014) Brain-derived neurotrophic factor in the amygdala mediates susceptibility to fear conditioning. Exp Neurol 255:19–29PubMedCrossRefGoogle Scholar
  25. Clem RL, Huganir RL (2010) Calcium-permeable AMPA receptor dynamics mediate fear memory erasure. Science 330:1108–1112PubMedPubMedCentralCrossRefGoogle Scholar
  26. Cole CJ, Mercaldo V, Restivo L, Yiu AP, Sekeres MJ, Han JH, Vetere G, Pekar T, Ross PJ, Neve RL, Frankland PW, Josselyn SA (2012) MEF2 negatively regulates learning-induced structural plasticity and memory formation. Nat Neurosci 15:1255–1264PubMedCrossRefGoogle Scholar
  27. Dahlhoff M, Siegmund A, Golub Y, Wolf E, Holsboer F, Wotjak CT (2010) AKT/GSK-3beta/beta-catenin signalling within hippocampus and amygdala reflects genetically determined differences in posttraumatic stress disorder like symptoms. Neuroscience 169:1216–1226PubMedCrossRefGoogle Scholar
  28. Davis S, Renaudineau S, Poirier R, Poucet B, Save E, Laroche S (2010) The formation and stability of recognition memory: what happens upon recall? Front Behav Neurosci 4:177PubMedPubMedCentralCrossRefGoogle Scholar
  29. de Kleine RA, Hendriks GJ, Kusters WJ, Broekman TG, van Minnen A (2012) A randomized placebo-controlled trial of D-cycloserine to enhance exposure therapy for posttraumatic stress disorder. Biol Psychiatry 71:962–968PubMedCrossRefGoogle Scholar
  30. de la Fuente V, Federman N, Fustinana MS, Zalcman G, Romano A (2014) Calcineurin phosphatase as a negative regulator of fear memory in hippocampus: control on nuclear factor-kappaB signaling in consolidation and reconsolidation. Hippocampus 24:1549–1561PubMedCrossRefGoogle Scholar
  31. de la Fuente V, Federman N, Zalcman G, Salles A, Freudenthal R, Romano A (2015) NF-kappaB transcription factor role in consolidation and reconsolidation of persistent memories. Front Mol Neurosci 8:50PubMedPubMedCentralGoogle Scholar
  32. Debiec J, Bush DE, LeDoux JE (2011) Noradrenergic enhancement of reconsolidation in the amygdala impairs extinction of conditioned fear in rats--a possible mechanism for the persistence of traumatic memories in PTSD. Depress Anxiety 28:186–193PubMedPubMedCentralCrossRefGoogle Scholar
  33. Dietrich JB (2013) The MEF2 family and the brain: from molecules to memory. Cell Tissue Res 352:179–190PubMedCrossRefGoogle Scholar
  34. Difede J, Cukor J, Wyka K, Olden M, Hoffman H, Lee FS, Altemus M (2014) D-cycloserine augmentation of exposure therapy for post-traumatic stress disorder: a pilot randomized clinical trial. Neuropsychopharmacology 39:1052–1058PubMedCrossRefGoogle Scholar
  35. Duclot F, Perez-Taboada I, Wright KN, Kabbaj M (2016) Prediction of individual differences in fear response by novelty seeking, and disruption of contextual fear memory reconsolidation by ketamine. Neuropharmacology 109:293–305PubMedPubMedCentralCrossRefGoogle Scholar
  36. Espejo PJ, Ortiz V, Martijena ID, Molina VA (2016) Stress-induced resistance to the fear memory labilization/reconsolidation process. Involvement of the basolateral amygdala complex. Neuropharmacology 109:349–356PubMedCrossRefGoogle Scholar
  37. Ferrer Monti RI, Alfei JM, Mugnaini M, Bueno AM, Beckers T, Urcelay GP, Molina VA (2017) A comparison of behavioral and pharmacological interventions to attenuate reactivated fear memories. Learn Mem 24:369–374PubMedCrossRefPubMedCentralGoogle Scholar
  38. First MB (2013) Diagnostic and statistical manual of mental disorders, 5th edition, and clinical utility. J Nerv Ment Dis 201:727–729PubMedCrossRefGoogle Scholar
  39. Flavell SW, Cowan CW, Kim TK, Greer PL, Lin Y, Paradis S, Griffith EC, Hu LS, Chen C, Greenberg ME (2006) Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science 311:1008–1012PubMedCrossRefGoogle Scholar
  40. Fortress AM, Schram SL, Tuscher JJ, Frick KM (2013) Canonical Wnt signaling is necessary for object recognition memory consolidation. J Neurosci 33:12619–12626PubMedCrossRefGoogle Scholar
  41. French PJ, O’Connor V, Jones MW, Davis S, Errington ML, Voss K, Truchet B, Wotjak C, Stean T, Doyere V, Maroun M, Laroche S, Bliss TV (2001) Subfield-specific immediate early gene expression associated with hippocampal long-term potentiation in vivo. Eur J Neurosci 13:968–976PubMedCrossRefGoogle Scholar
  42. Freudenthal R, Locatelli F, Hermitte G, Maldonado H, Lafourcade C, Delorenzi A, Romano A (1998) Kappa-B like DNA-binding activity is enhanced after spaced training that induces long-term memory in the crab Chasmagnathus. Neurosci Lett 242:143–146PubMedCrossRefGoogle Scholar
  43. Freudenthal R, Romano A, Routtenberg A (2004) Transcription factor NF-kappaB activation after in vivo perforant path LTP in mouse hippocampus. Hippocampus 14:677–683PubMedCrossRefGoogle Scholar
  44. Gamache K, Pitman RK, Nader K (2012) Preclinical evaluation of reconsolidation blockade by clonidine as a potential novel treatment for posttraumatic stress disorder. Neuropsychopharmacology Official Publication of the American College of Neuropsychopharmacology 37:2789PubMedPubMedCentralCrossRefGoogle Scholar
  45. Gazarini L, Stern CA, Carobrez AP, Bertoglio LJ (2013) Enhanced noradrenergic activity potentiates fear memory consolidation and reconsolidation by differentially recruiting alpha1- and beta-adrenergic receptors. Learn Mem 20:210–219PubMedCrossRefGoogle Scholar
  46. Giachero M, Bustos SG, Calfa G, Molina VA (2013) A BDNF sensitive mechanism is involved in the fear memory resulting from the interaction between stress and the retrieval of an established trace. Learn Mem 20:245–255PubMedCrossRefGoogle Scholar
  47. Golier JA, Caramanica K, Michaelides AC, Makotkine I, Schmeidler J, Harvey PD, Yehuda R (2016) A randomized, double-blind, placebo-controlled, crossover trial of mifepristone in Gulf War veterans with chronic multisymptom illness. Psychoneuroendocrinology 64:22–30PubMedCrossRefGoogle Scholar
  48. Gould TD, Picchini AM, Einat H, Manji HK (2006) Targeting glycogen synthase kinase-3 in the CNS: implications for the development of new treatments for mood disorders. Curr Drug Targets 7:1399–1409PubMedCrossRefGoogle Scholar
  49. Gumbiner BM (1996) Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell 84:345–357PubMedCrossRefGoogle Scholar
  50. Gundersen K (2011) Excitation-transcription coupling in skeletal muscle: the molecular pathways of exercise. Biol Rev Camb Philos Soc 86:564–600PubMedPubMedCentralCrossRefGoogle Scholar
  51. Hall J, Thomas KL, Everitt BJ (2001a) Cellular imaging of zif268 expression in the hippocampus and amygdala during contextual and cued fear memory retrieval: selective activation of hippocampal CA1 neurons during the recall of contextual memories. J Neurosci 21:2186–2193PubMedCrossRefGoogle Scholar
  52. Hall J, Thomas KL, Everitt BJ (2001b) Fear memory retrieval induces CREB phosphorylation and Fos expression within the amygdala. Eur J Neurosci 13:1453–1458PubMedCrossRefGoogle Scholar
  53. Han JH, Kushner SA, Yiu AP, Cole CJ, Matynia A, Brown RA, Neve RL, Guzowski JF, Silva AJ, Josselyn SA (2007) Neuronal competition and selection during memory formation. Science 316:457–460PubMedCrossRefGoogle Scholar
  54. Hellemans KG, Everitt BJ, Lee JL (2006) Disrupting reconsolidation of conditioned withdrawal memories in the basolateral amygdala reduces suppression of heroin seeking in rats. J Neurosci 26:12694–12699PubMedCrossRefGoogle Scholar
  55. Hoffman AN, Parga A, Paode PR, Watterson LR, Nikulina EM, Hammer RP Jr, Conrad CD (2015) Chronic stress enhanced fear memories are associated with increased amygdala zif268 mRNA expression and are resistant to reconsolidation. Neurobiol Learn Mem 120:61–68PubMedPubMedCentralCrossRefGoogle Scholar
  56. Hofmann SG, Smits JA, Rosenfield D, Simon N, Otto MW, Meuret AE, Marques L, Fang A, Tart C, Pollack MH (2013) D-Cycloserine as an augmentation strategy with cognitive-behavioral therapy for social anxiety disorder. Am J Psychiatry 170:751–758PubMedPubMedCentralCrossRefGoogle Scholar
  57. Hong JG, Kim DH, Lee CH, Park SJ, Kim JM, Cai M, Jang DS, Ryu JH (2012) GSK-3β activity in the hippocampus is required for memory retrieval. Neurobiol Learn Mem 98:122–129PubMedCrossRefGoogle Scholar
  58. Kida S, Josselyn SA, Pena de Ortiz S, Kogan JH, Chevere I, Masushige S, Silva AJ (2002) CREB required for the stability of new and reactivated fear memories. Nat Neurosci 5:348–355PubMedCrossRefGoogle Scholar
  59. Kim R, Moki R, Kida S (2011) Molecular mechanisms for the destabilization and restabilization of reactivated spatial memory in the Morris water maze. Mol Brain 4:9PubMedPubMedCentralCrossRefGoogle Scholar
  60. Kim J, Kwon JT, Kim HS, Han JH (2013) CREB and neuronal selection for memory trace. Front Neural Circuits 7:44PubMedPubMedCentralCrossRefGoogle Scholar
  61. Kim J, Kwon JT, Kim HS, Josselyn SA, Han JH (2014) Memory recall and modifications by activating neurons with elevated CREB. Nat Neurosci 17:65–72PubMedCrossRefGoogle Scholar
  62. Kimura T, Yamashita S, Nakao S, Park J, Murayama M, Mizoroki T, Yoshiike Y, Sahara N, Takashima A (2008) GSK-3beta is required for memory reconsolidation in adult brain. PLoS One 3:e3540PubMedPubMedCentralCrossRefGoogle Scholar
  63. Kindt M, Soeter M (2013) Reconsolidation in a human fear conditioning study: a test of extinction as updating mechanism. Biol Psychol 92:43–50PubMedCrossRefGoogle Scholar
  64. Kindt M, Soeter M, Vervliet B (2009) Beyond extinction: erasing human fear responses and preventing the return of fear. Nat Neurosci 12:256–258PubMedCrossRefGoogle Scholar
  65. Kindt M, Soeter M, Sevenster D (2014) Disrupting reconsolidation of fear memory in humans by a noradrenergic beta-blocker. J Vis Exp.
  66. Kojima N, Borlikova G, Sakamoto T, Yamada K, Ikeda T, Itohara S, Niki H, Endo S (2008) Inducible cAMP early repressor acts as a negative regulator for kindling epileptogenesis and long-term fear memory. J Neurosci 28:6459–6472PubMedCrossRefGoogle Scholar
  67. Kroes MC, Tona KD, den Ouden HE, Vogel S, van Wingen GA, Fernandez G (2016) How administration of the beta-blocker propranolol before extinction can prevent the return of fear. Neuropsychopharmacology 41:1569–1578PubMedCrossRefGoogle Scholar
  68. Lee JL (2010) Memory reconsolidation mediates the updating of hippocampal memory content. Front Behav Neurosci 4:168PubMedPubMedCentralCrossRefGoogle Scholar
  69. Lee JL, Hynds RE (2013) Divergent cellular pathways of hippocampal memory consolidation and reconsolidation. Hippocampus 23:233–244PubMedCrossRefGoogle Scholar
  70. Lee JL, Everitt BJ, Thomas KL (2004) Independent cellular processes for hippocampal memory consolidation and reconsolidation. Science 304:839–843PubMedCrossRefGoogle Scholar
  71. Lee JL, Milton AL, Everitt BJ (2006a) Cue-induced cocaine seeking and relapse are reduced by disruption of drug memory reconsolidation. J Neurosci 26:5881–5887PubMedCrossRefGoogle Scholar
  72. Lee JL, Milton AL, Everitt BJ (2006b) Reconsolidation and extinction of conditioned fear: inhibition and potentiation. J Neurosci 26:10051–10056PubMedCrossRefGoogle Scholar
  73. Liu JF, Yang C, Deng JH, Yan W, Wang HM, Luo YX, Shi HS, Meng SQ, Chai BS, Fang Q, Chai N, Xue YX, Sun J, Chen C, Wang XY, Wang JS, Lu L (2015) Role of hippocampal beta-adrenergic and glucocorticoid receptors in the novelty-induced enhancement of fear extinction. J Neurosci 35:8308–8321PubMedCrossRefGoogle Scholar
  74. Lubin FD, Sweatt JD (2007) The IkappaB kinase regulates chromatin structure during reconsolidation of conditioned fear memories. Neuron 55:942–957PubMedPubMedCentralCrossRefGoogle Scholar
  75. Lv XF, Sun LL, Cui CL, Han JS (2015) NAc shell Arc/Arg3.1 protein mediates reconsolidation of morphine CPP by increased GluR1 cell surface expression: activation of ERK-coupled CREB is required. Int J Neuropsychopharmacol 18Google Scholar
  76. Ma Q, Telese F (2015) Genome-wide epigenetic analysis of MEF2A and MEF2C transcription factors in mouse cortical neurons. Commun Integr Biol 8:e1087624PubMedPubMedCentralCrossRefGoogle Scholar
  77. Machado I, Gonzalez PV, Vilcaes A, Carniglia L, Schioth HB, Lasaga M, Scimonelli TN (2015) Interleukin-1beta-induced memory reconsolidation impairment is mediated by a reduction in glutamate release and zif268 expression and alpha-melanocyte-stimulating hormone prevented these effects. Brain Behav Immun 46:137–146PubMedCrossRefGoogle Scholar
  78. Magee JC, Johnston D (1995) Synaptic activation of voltage-gated channels in the dendrites of hippocampal pyramidal neurons. Science 268:301–304PubMedCrossRefGoogle Scholar
  79. Maguschak KA, Ressler KJ (2008) Beta-catenin is required for memory consolidation. Nat Neurosci 11:1319–1326PubMedPubMedCentralCrossRefGoogle Scholar
  80. Maguschak KA, Ressler KJ (2011) Wnt signaling in amygdala-dependent learning and memory. J Neurosci 31:13057–13067PubMedPubMedCentralCrossRefGoogle Scholar
  81. Maguschak KA, Ressler KJ (2012) The dynamic role of beta-catenin in synaptic plasticity. Neuropharmacology 62:78–88PubMedCrossRefGoogle Scholar
  82. Makkar SR, Zhang SQ, Cranney J (2010) Behavioral and neural analysis of GABA in the acquisition, consolidation, reconsolidation, and extinction of fear memory. Neuropsychopharmacology 35:1625–1652PubMedPubMedCentralCrossRefGoogle Scholar
  83. Mamiya N, Fukushima H, Suzuki A, Matsuyama Z, Homma S, Frankland PW, Kida S (2009) Brain region-specific gene expression activation required for reconsolidation and extinction of contextual fear memory. J Neurosci 29:402–413PubMedCrossRefGoogle Scholar
  84. Mao Z, Bonni A, Xia F, Nadal-Vicens M, Greenberg ME (1999) Neuronal activity-dependent cell survival mediated by transcription factor MEF2. Science 286:785–790PubMedCrossRefGoogle Scholar
  85. Matrisciano F, Busceti CL, Bucci D, Orlando R, Caruso A, Molinaro G, Cappuccio I, Riozzi B, Gradini R, Motolese M (2011) Induction of the Wnt antagonist Dickkopf-1 is involved in stress-induced hippocampal damage. PLoS One 6:126–143CrossRefGoogle Scholar
  86. Mattson MP, Meffert MK (2006) Roles for NF-kappaB in nerve cell survival, plasticity, and disease. Cell Death Differ 13:852–860PubMedCrossRefGoogle Scholar
  87. McGaugh JL (2000) Memory--a century of consolidation. Science 287:248–251PubMedCrossRefGoogle Scholar
  88. McGhee LL, Maani CV, Garza TH, Desocio PA, Gaylord KM, Black IH (2009) The effect of propranolol on posttraumatic stress disorder in burned service members. J Burn Care Res 30:92–97PubMedCrossRefGoogle Scholar
  89. Meffert MK, Chang JM, Wiltgen BJ, Fanselow MS, Baltimore D (2003) NF-kappa B functions in synaptic signaling and behavior. Nat Neurosci 6:1072–1078PubMedCrossRefGoogle Scholar
  90. Merlo E, Romano A (2008) Memory extinction entails the inhibition of the transcription factor NF-kappaB. PLoS One 3:e3687PubMedPubMedCentralCrossRefGoogle Scholar
  91. Merlo E, Freudenthal R, Maldonado H, Romano A (2005) Activation of the transcription factor NF-kappaB by retrieval is required for long-term memory reconsolidation. Learn Mem 12:23–29PubMedPubMedCentralCrossRefGoogle Scholar
  92. Milekic MH, Brown SD, Castellini C, Alberini CM (2006) Persistent disruption of an established morphine conditioned place preference. J Neurosci 26:3010–3020PubMedCrossRefGoogle Scholar
  93. Milton AL, Lee JL, Butler VJ, Gardner R, Everitt BJ (2008) Intra-amygdala and systemic antagonism of NMDA receptors prevents the reconsolidation of drug-associated memory and impairs subsequently both novel and previously acquired drug-seeking behaviors. J Neurosci 28:8230–8237PubMedCrossRefGoogle Scholar
  94. Monfils MH, Cowansage KK, Klann E, LeDoux JE (2009) Extinction-reconsolidation boundaries: key to persistent attenuation of fear memories. Science 324:951–955PubMedPubMedCentralCrossRefGoogle Scholar
  95. Morice E, Farley S, Poirier R, Dallerac G, Chagneau C, Pannetier S, Hanauer A, Davis S, Vaillend C, Laroche S (2013) Defective synaptic transmission and structure in the dentate gyrus and selective fear memory impairment in the Rsk2 mutant mouse model of Coffin-Lowry syndrome. Neurobiol Dis 58:156–168PubMedCrossRefGoogle Scholar
  96. Mouravlev A, Dunning J, Young D, During MJ (2006) Somatic gene transfer of cAMP response element-binding protein attenuates memory impairment in aging rats. Proc Natl Acad Sci U S A 103:4705–4710PubMedPubMedCentralCrossRefGoogle Scholar
  97. Murase S, Mosser E, Schuman EM (2002) Depolarization drives beta-Catenin into neuronal spines promoting changes in synaptic structure and function. Neuron 35:91–105PubMedCrossRefGoogle Scholar
  98. Muravieva EV, Alberini CM (2010) Limited efficacy of propranolol on the reconsolidation of fear memories. Learn Mem 17:306–313PubMedPubMedCentralCrossRefGoogle Scholar
  99. Muschamp JW, Van’t Veer A, Parsegian A, Gallo MS, Chen M, Neve RL, Meloni EG, Carlezon WA (2011) Activation of CREB in the nucleus accumbens shell produces anhedonia and resistance to extinction of fear in rats. J Neurosci 31:3095–3103PubMedPubMedCentralCrossRefGoogle Scholar
  100. Nader K, Einarsson EO (2010) Memory reconsolidation: an update. Ann N Y Acad Sci 1191:27–41PubMedCrossRefGoogle Scholar
  101. Nader K, Hardt O (2009) A single standard for memory: the case for reconsolidation. Nat Rev Neurosci 10:224–234PubMedCrossRefGoogle Scholar
  102. Nader K, Schafe GE, Le Doux JE (2000) Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406:722–726PubMedCrossRefGoogle Scholar
  103. Nelson WJ, Nusse R (2004) Convergence of Wnt, beta-catenin, and cadherin pathways. Science 303:1483–1487PubMedPubMedCentralCrossRefGoogle Scholar
  104. Nimchinsky EA, Sabatini BL, Svoboda K (2002) Structure and function of dendritic spines. Annu Rev Physiol 64:313–353PubMedCrossRefGoogle Scholar
  105. Ortiz V, Molina VA, Martijena ID (2016) Effect of a positive reinforcing stimulus on fear memory reconsolidation in ethanol withdrawn rats: Influence of d-cycloserine. Behav Brain Res 315:66–70PubMedCrossRefGoogle Scholar
  106. Parra-Damas A, Chen M, Enriquez-Barreto L, Ortega L, Acosta S, Perna JC, Fullana MN, Aguilera J, Rodriguez-Alvarez J, Saura CA (2017) CRTC1 function during memory encoding is disrupted in neurodegeneration. Biol Psychiatry 81:111–123PubMedCrossRefGoogle Scholar
  107. Pavlova IV, Rysakova MP (2014) Effects of intrabasolateral amygdala infusions of GABAA-receptor agonist and antagonist on expression and extinction of conditioned fear in rats with different freezing duration. Zh Vyssh Nerv Deiat Im I P Pavlova 64:460–473PubMedGoogle Scholar
  108. Penzo MA, Robert V, Tucciarone J, De Bundel D, Wang M, Van Aelst L, Darvas M, Parada LF, Palmiter RD, He M, Huang ZJ, Li B (2015) The paraventricular thalamus controls a central amygdala fear circuit. Nature 519:455–459PubMedPubMedCentralCrossRefGoogle Scholar
  109. Perkins ND (2007) Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 8:49–62PubMedCrossRefGoogle Scholar
  110. Pitman RK (1988) Post-traumatic stress disorder, conditioning, and network theory. Psychiatr Ann 8:182–189CrossRefGoogle Scholar
  111. Pitman RK (2011) Will reconsolidation blockade offer a novel treatment for posttraumatic stress disorder? Front Behav Neurosci 5:11PubMedPubMedCentralCrossRefGoogle Scholar
  112. Pitman RK, Sanders KM, Zusman RM, Healy AR, Cheema F, Lasko NB, Cahill L, Orr SP (2002) Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry 51:189–192PubMedCrossRefGoogle Scholar
  113. Pitman RK, Milad MR, Igoe SA, Vangel MG, Orr SP, Tsareva A, Gamache K, Nader K (2011) Systemic mifepristone blocks reconsolidation of cue-conditioned fear; propranolol prevents this effect. Behav Neurosci 125:632–638PubMedCrossRefGoogle Scholar
  114. Rashid AJ, Cole CJ, Josselyn SA (2014) Emerging roles for MEF2 transcription factors in memory. Genes Brain Behav 13:118–125PubMedCrossRefGoogle Scholar
  115. Ren J, Li X, Zhang X, Li M, Wang Y, Ma Y (2013) The effects of intra-hippocampal microinfusion of D-cycloserine on fear extinction, and the expression of NMDA receptor subunit NR2B and neurogenesis in the hippocampus in rats. Prog Neuropsychopharmacol Biol Psychiatry 44:257–264PubMedCrossRefGoogle Scholar
  116. Rothbaum BO, Kearns MC, Price M, Malcoun E, Davis M, Ressler KJ, Lang D, Houry D (2012) Early intervention may prevent the development of posttraumatic stress disorder: a randomized pilot civilian study with modified prolonged exposure. Biol Psychiatry 72:957–963PubMedPubMedCentralCrossRefGoogle Scholar
  117. Saitoh A, Akagi K, Oka JI, Yamada M (2017) Post-reexposure administration of D-cycloserine facilitates reconsolidation of contextual conditioned fear memory in rats. J Neural Transm (Vienna) 124:583–587CrossRefGoogle Scholar
  118. Sara SJ (2000) Retrieval and reconsolidation: toward a neurobiology of remembering. Learn Mem 7:73–84PubMedCrossRefGoogle Scholar
  119. Saridogan GE, Aykac A, Cabadak H, Cerit C, Caliskan M, Goren MZ (2015) D-Cycloserine acts via increasing the GluN1 protein expressions in the frontal cortex and decreases the avoidance and risk assessment behaviors in a rat traumatic stress model. Behav Brain Res 293:227–233PubMedCrossRefGoogle Scholar
  120. Schiller D, Monfils MH, Raio CM, Johnson DC, Ledoux JE, Phelps EA (2010) Preventing the return of fear in humans using reconsolidation update mechanisms. Nature 463:49–53PubMedCrossRefGoogle Scholar
  121. Sekeres MJ, Mercaldo V, Richards B, Sargin D, Mahadevan V, Woodin MA, Frankland PW, Josselyn SA (2012) Increasing CRTC1 function in the dentate gyrus during memory formation or reactivation increases memory strength without compromising memory quality. J Neurosci 32:17857–17868PubMedCrossRefGoogle Scholar
  122. Shalizi A, Gaudillière B, Yuan Z, Stegmüller J, Shirogane T, Ge Q, Tan Y, Schulman B, Harper JW, Bonni A (2006) A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation. Science 311:1012–1017PubMedCrossRefGoogle Scholar
  123. Shi XD, Miller JS, Harper LJ, Poole RL, Gould TJ, Unterwald EM (2014) Reactivation of cocaine reward memory engages the Akt/GSK3/mTOR signaling pathway and can be disrupted by GSK3 inhibition. Psychopharmacology 231:3109–3118PubMedPubMedCentralCrossRefGoogle Scholar
  124. Si J, Yang J, Xue L, Yang C, Luo Y, Shi H, Lu L (2012) Activation of NF-kappaB in basolateral amygdala is required for memory reconsolidation in auditory fear conditioning. PLoS One 7:e43973PubMedPubMedCentralCrossRefGoogle Scholar
  125. Signor C, Girardi BA, Lorena Wendel A, Fruhauf PKS, Pillat MM, Ulrich H, Mello CF, Rubin MA (2017) Spermidine improves the persistence of reconsolidated fear memory and neural differentiation in vitro: Involvement of BDNF. Neurobiol Learn Mem 140:82–91PubMedCrossRefGoogle Scholar
  126. Singewald N, Schmuckermair C, Whittle N, Holmes A, Ressler KJ (2015) Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders. Pharmacol Ther 149:150–190PubMedCrossRefGoogle Scholar
  127. Snow WM, Stoesz BM, Kelly DM, Albensi BC (2014) Roles for NF-kappaB and gene targets of NF-kappaB in synaptic plasticity, memory, and navigation. Mol Neurobiol 49:757–770PubMedCrossRefGoogle Scholar
  128. Stafford JM, Lattal KM (2009) Direct comparisons of the size and persistence of anisomycin-induced consolidation and reconsolidation deficits. Learn Mem 16:494–503PubMedPubMedCentralCrossRefGoogle Scholar
  129. Stafford JM, Maughan DK, Ilioi EC, Lattal KM (2013) Exposure to a fearful context during periods of memory plasticity impairs extinction via hyperactivation of frontal-amygdalar circuits. Learn Mem 20:156–163PubMedPubMedCentralCrossRefGoogle Scholar
  130. Steenen SA, van Wijk AJ, van der Heijden GJ, van Westrhenen R, de Lange J, de Jongh A (2016) Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis. J Psychopharmacol 30:128–139PubMedPubMedCentralCrossRefGoogle Scholar
  131. Stern CA, Gazarini L, Vanvossen AC, Hames MS, Bertoglio LJ (2014) Activity in prelimbic cortex subserves fear memory reconsolidation over time. Learn Mem 21:14–20PubMedCentralCrossRefGoogle Scholar
  132. Taherian F, Vafaei AA, Vaezi GH, Eskandarian S, Kashef A, Rashidy-Pour A (2014) Propranolol-induced impairment of contextual fear memory reconsolidation in rats: a similar effect on weak and strong recent and remote memories. Basic Clin Neurosci 5:231–239PubMedPubMedCentralGoogle Scholar
  133. Tai CY, Mysore SP, Chiu C, Schuman EM (2007) Activity-regulated N-cadherin endocytosis. Neuron 54:771–785PubMedCrossRefGoogle Scholar
  134. Taubenfeld SM, Riceberg JS, New AS, Alberini CM (2009) Preclinical assessment for selectively disrupting a traumatic memory via postretrieval inhibition of glucocorticoid receptors. Biol Psychiatry 65:249–257PubMedCrossRefGoogle Scholar
  135. Tedesco V, Roquet RF, DeMis J, Chiamulera C, Monfils MH (2014) Extinction, applied after retrieval of auditory fear memory, selectively increases zinc-finger protein 268 and phosphorylated ribosomal protein S6 expression in prefrontal cortex and lateral amygdala. Neurobiol Learn Mem 115:78–85PubMedCrossRefGoogle Scholar
  136. Theberge FR, Milton AL, Belin D, Lee JL, Everitt BJ (2010) The basolateral amygdala and nucleus accumbens core mediate dissociable aspects of drug memory reconsolidation. Learn Mem 17:444–453PubMedPubMedCentralCrossRefGoogle Scholar
  137. Thomas KL, Hall J, Everitt BJ (2002) Cellular imaging with zif268 expression in the rat nucleus accumbens and frontal cortex further dissociates the neural pathways activated following the retrieval of contextual and cued fear memory. Eur J Neurosci 16:1789–1796PubMedCrossRefGoogle Scholar
  138. Thomas KL, Arroyo M, Everitt BJ (2003) Induction of the learning and plasticity-associated gene Zif268 following exposure to a discrete cocaine-associated stimulus. Eur J Neurosci 17:1964–1972PubMedCrossRefGoogle Scholar
  139. Trent S, Barnes P, Hall J, Thomas KL (2015) Rescue of long-term memory after reconsolidation blockade. Nat Commun 6:7897PubMedPubMedCentralCrossRefGoogle Scholar
  140. Tronel S, Alberini CM (2007) Persistent disruption of a traumatic memory by postretrieval inactivation of glucocorticoid receptors in the amygdala. Biol Psychiatry 62:33–39PubMedPubMedCentralCrossRefGoogle Scholar
  141. Tronson NC, Wiseman SL, Neve RL, Nestler EJ, Olausson P, Taylor JR (2012) Distinctive roles for amygdalar CREB in reconsolidation and extinction of fear memory. Learn Mem 19:178–181PubMedPubMedCentralCrossRefGoogle Scholar
  142. Vetere G, Restivo L, Cole CJ, Ross PJ, Ammassari-Teule M, Josselyn SA, Frankland PW (2011) Spine growth in the anterior cingulate cortex is necessary for the consolidation of contextual fear memory. Proc Natl Acad Sci U S A 108:8456–8460PubMedPubMedCentralCrossRefGoogle Scholar
  143. Vetere G, Piserchia V, Borreca A, Novembre G, Aceti M, Ammassari-Teule M (2013) Reactivating fear memory under propranolol resets pre-trauma levels of dendritic spines in basolateral amygdala but not dorsal hippocampus neurons. Front Behav Neurosci 7:211PubMedPubMedCentralCrossRefGoogle Scholar
  144. Vetere G, Barbato C, Pezzola S, Frisone P, Aceti M, Ciotti M, Cogoni C, Ammassari-Teule M, Ruberti F (2014) Selective inhibition of miR-92 in hippocampal neurons alters contextual fear memory. Hippocampus 24:1458–1465PubMedCrossRefGoogle Scholar
  145. Wada A (2009) Lithium and neuropsychiatric therapeutics: neuroplasticity via glycogen synthase kinase-3beta, beta-catenin, and neurotrophin cascades. J Pharmacol Sci 110:14–28PubMedCrossRefGoogle Scholar
  146. Walker MP, Brakefield T, Hobson JA, Stickgold R (2003) Dissociable stages of human memory consolidation and reconsolidation. Nature 425:616–620PubMedCrossRefGoogle Scholar
  147. Wood NE, Rosasco ML, Suris AM, Spring JD, Marin MF, Lasko NB, Goetz JM, Fischer AM, Orr SP, Pitman RK (2015) Pharmacological blockade of memory reconsolidation in posttraumatic stress disorder: three negative psychophysiological studies. Psychiatry Res 225:31–39PubMedCrossRefGoogle Scholar
  148. Wu IT, Tang TH, Ko MC, Chiu CY, Lu KT (2015) Amygdaloid zif268 participated in the D-cycloserine facilitation effect on the extinction of conditioned fear. Psychopharmacology 232:3809–3819PubMedCrossRefGoogle Scholar
  149. Xu N, Zhou WJ, Wang Y, Huang SH, Li X, Chen ZY (2015) Hippocampal Wnt3a is necessary and sufficient for contextual fear memory acquisition and consolidation. Cereb Cortex 25:4062–4075PubMedCrossRefGoogle Scholar
  150. Yamamoto Y, Verma UN, Prajapati S, Kwak YT, Gaynor RB (2003) Histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression. Nature 423:655–659PubMedCrossRefGoogle Scholar
  151. Yamamoto S, Morinobu S, Fuchikami M, Kurata A, Kozuru T, Yamawaki S (2008) Effects of single prolonged stress and D-cycloserine on contextual fear extinction and hippocampal NMDA receptor expression in a rat model of PTSD. Neuropsychopharmacology 33:2108–2116PubMedCrossRefGoogle Scholar
  152. Yang J, Yu J, Jia X, Zhu W, Zhao L, Li S, Xu C, Yang C, Wu P, Lu L (2011) Inhibition of nuclear factor-kappaB impairs reconsolidation of morphine reward memory in rats. Behav Brain Res 216:592–596PubMedCrossRefGoogle Scholar
  153. Yin JC, Wallach JS, Del Vecchio M, Wilder EL, Zhou H, Quinn WG, Tully T (1994) Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila. Cell 79:49–58PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Military Psychology, College of PsychologyArmy Medical UniversityChongqingChina
  2. 2.Forth Battalion of Cadet BrigadeArmy Medical UniversityChongqingChina
  3. 3.Medical CompanyTroops 95848 of People’s Liberation ArmyXiaoganChina
  4. 4.Department of FundamentalArmy Logistical University of PLAChongqingChina

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