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Volumn 4, Issue NOV, 2013, Pages

Regulating critical period plasticity: Insight from the visual system to fear circuitry for therapeutic interventions

Author keywords

critical period; Fear erasure; HDAC inhibitors; Lynx1; Perineuronal nets; Reconsolidation update; Visual cortex plasticity

Indexed keywords

BUTYRIC ACID; CHOLINESTERASE INHIBITOR; FLUOXETINE; HISTONE DEACETYLASE INHIBITOR; LYNX PROTEIN; MEMBRANE PROTEIN; MYELIN; NICOTINIC RECEPTOR; PROTEIN NOGO; SEROTONIN UPTAKE INHIBITOR; TRICHOSTATIN A; UNCLASSIFIED DRUG; VALPROIC ACID;

EID: 84889685633     PISSN: None     EISSN: 16640640     Source Type: Journal    
DOI: 10.3389/fpsyt.2013.00146     Document Type: Review
Times cited : (68)

References (85)
  • 1
    • 3943087045 scopus 로고    scopus 로고
    • Critical period regulation
    • doi:10.1146/annurev.neuro.27.070203.144327
    • Hensch TK. Critical period regulation. Annu Rev Neurosci (2004) 27:549-79. doi:10.1146/annurev.neuro.27.070203.144327
    • (2004) Annu Rev Neurosci , vol.27 , pp. 549-579
    • Hensch, T.K.1
  • 2
    • 6944241340 scopus 로고    scopus 로고
    • Sensitive periods in the development of the brain and behavior
    • doi:10.1162/0898929042304796
    • Knudsen EI. Sensitive periods in the development of the brain and behavior. J Cogn Neurosci (2004) 16:1412-25. doi:10.1162/0898929042304796
    • (2004) J Cogn Neurosci , vol.16 , pp. 1412-1425
    • Knudsen, E.I.1
  • 3
    • 0019997224 scopus 로고
    • Postnatal development of the visual cortex and the influence of environment
    • doi:10.1038/299583a0
    • Wiesel TN. Postnatal development of the visual cortex and the influence of environment. Nature (1982) 299:583-91. doi:10.1038/299583a0
    • (1982) Nature , vol.299 , pp. 583-591
    • Wiesel, T.N.1
  • 4
    • 29544445007 scopus 로고    scopus 로고
    • Amblyopia: diagnostic and therapeutic options
    • doi:10.1016/j.ajo.2005.07.060
    • Wu C, Hunter DG. Amblyopia: diagnostic and therapeutic options. Am J Ophthalmol (2006) 141:175-84. doi:10.1016/j.ajo.2005.07.060
    • (2006) Am J Ophthalmol , vol.141 , pp. 175-184
    • Wu, C.1    Hunter, D.G.2
  • 5
    • 0037232411 scopus 로고    scopus 로고
    • Developmental plasticity of mouse visual acuity
    • doi:10.1046/j.1460-9568.2003.02420.x
    • Prusky GT, Douglas RM. Developmental plasticity of mouse visual acuity. Eur J Neurosci (2003) 17:167-73. doi:10.1046/j.1460-9568.2003.02420.x
    • (2003) Eur J Neurosci , vol.17 , pp. 167-173
    • Prusky, G.T.1    Douglas, R.M.2
  • 6
    • 0033791643 scopus 로고    scopus 로고
    • Experience-dependent plasticity of visual acuity in rats
    • doi:10.1046/j.1460-9568.2000.00236.x
    • Prusky GT, West PW, Douglas RM. Experience-dependent plasticity of visual acuity in rats. Eur J Neurosci (2000) 12:3781-6. doi:10.1046/j.1460-9568.2000.00236.x
    • (2000) Eur J Neurosci , vol.12 , pp. 3781-3786
    • Prusky, G.T.1    West, P.W.2    Douglas, R.M.3
  • 7
    • 27644551416 scopus 로고    scopus 로고
    • Critical period plasticity in local cortical circuits
    • Hensch TK. Critical period plasticity in local cortical circuits. Nat Rev Neurosci (2005) 6(11):877-88.
    • (2005) Nat Rev Neurosci , vol.6 , Issue.11 , pp. 877-888
    • Hensch, T.K.1
  • 8
    • 46549086820 scopus 로고    scopus 로고
    • Critical period revisited: impact on vision
    • doi:10.1016/j.conb.2008.05.009
    • Morishita H, Hensch TK. Critical period revisited: impact on vision. Curr Opin Neurobiol (2008) 18:101-7. doi:10.1016/j.conb.2008.05.009
    • (2008) Curr Opin Neurobiol , vol.18 , pp. 101-107
    • Morishita, H.1    Hensch, T.K.2
  • 9
    • 80052262171 scopus 로고    scopus 로고
    • A critical period for auditory thalamocortical connectivity
    • doi:10.1038/nn.2882
    • Barkat TR, Polley DB, Hensch TK. A critical period for auditory thalamocortical connectivity. Nat Neurosci (2011) 14:1189-94. doi:10.1038/nn.2882
    • (2011) Nat Neurosci , vol.14 , pp. 1189-1194
    • Barkat, T.R.1    Polley, D.B.2    Hensch, T.K.3
  • 10
    • 69949184925 scopus 로고    scopus 로고
    • Perineuronal nets protect fear memories from erasure
    • doi:10.1126/science.1174146
    • Gogolla N, Caroni P, Luthi A, Herry C. Perineuronal nets protect fear memories from erasure. Science (2009) 325:1258-61. doi:10.1126/science.1174146
    • (2009) Science , vol.325 , pp. 1258-1261
    • Gogolla, N.1    Caroni, P.2    Luthi, A.3    Herry, C.4
  • 11
    • 84872247467 scopus 로고    scopus 로고
    • Critical period for acoustic preference in mice
    • doi:10.1073/pnas.1200705109
    • Yang EJ, Lin EW, Hensch TK. Critical period for acoustic preference in mice. Proc Natl Acad Sci USA (2012) 109(Suppl 2):17213-20. doi:10.1073/pnas.1200705109
    • (2012) Proc Natl Acad Sci USA , vol.109 , Issue.SUPPL. 2 , pp. 17213-17220
    • Yang, E.J.1    Lin, E.W.2    Hensch, T.K.3
  • 12
    • 84870562937 scopus 로고    scopus 로고
    • Ontogeny of contextual fear memory formation, specificity, and persistence in mice
    • doi:10.1101/lm.027581.112
    • Akers KG, Arruda-Carvalho M, Josselyn SA, Frankland PW. Ontogeny of contextual fear memory formation, specificity, and persistence in mice. Learn Mem (2012) 19:598-604. doi:10.1101/lm.027581.112
    • (2012) Learn Mem , vol.19 , pp. 598-604
    • Akers, K.G.1    Arruda-Carvalho, M.2    Josselyn, S.A.3    Frankland, P.W.4
  • 13
    • 34249341680 scopus 로고    scopus 로고
    • A developmental dissociation in reinstatement of an extinguished fear response in rats
    • doi:10.1016/j.nlm.2007.03.004
    • Kim JH, Richardson R. A developmental dissociation in reinstatement of an extinguished fear response in rats. Neurobiol Learn Mem (2007) 88:48-57. doi:10.1016/j.nlm.2007.03.004
    • (2007) Neurobiol Learn Mem , vol.88 , pp. 48-57
    • Kim, J.H.1    Richardson, R.2
  • 14
    • 33847316077 scopus 로고    scopus 로고
    • A developmental dissociation of context and GABA effects on extinguished fear in rats
    • doi:10.1037/0735-7044.121.1.131
    • Kim JH, Richardson R. A developmental dissociation of context and GABA effects on extinguished fear in rats. Behav Neurosci (2007) 121:131-9. doi:10.1037/0735-7044.121.1.131
    • (2007) Behav Neurosci , vol.121 , pp. 131-139
    • Kim, J.H.1    Richardson, R.2
  • 15
    • 74749097423 scopus 로고    scopus 로고
    • New findings on extinction of conditioned fear early in development: theoretical and clinical implications
    • doi:10.1016/j.biopsych.2009.09.003
    • Kim JH, Richardson R. New findings on extinction of conditioned fear early in development: theoretical and clinical implications. Biol Psychiatry (2010) 67:297-303. doi:10.1016/j.biopsych.2009.09.003
    • (2010) Biol Psychiatry , vol.67 , pp. 297-303
    • Kim, J.H.1    Richardson, R.2
  • 17
    • 70349782163 scopus 로고    scopus 로고
    • Consequences of extinction training on associative and non-associative fear in a mouse model of Posttraumatic Stress Disorder (PTSD)
    • doi:10.1016/j.bbr.2009.08.019
    • Golub Y, Mauch CP, Dahlhoff M, Wotjak CT. Consequences of extinction training on associative and non-associative fear in a mouse model of Posttraumatic Stress Disorder (PTSD). Behav Brain Res (2009) 205:544-9. doi:10.1016/j.bbr.2009.08.019
    • (2009) Behav Brain Res , vol.205 , pp. 544-549
    • Golub, Y.1    Mauch, C.P.2    Dahlhoff, M.3    Wotjak, C.T.4
  • 18
    • 84863860428 scopus 로고    scopus 로고
    • Posttraumatic stress disorder: shifting toward a developmental framework
    • doi:10.1016/j.chc.2012.05.004
    • Carrion VG, Kletter H. Posttraumatic stress disorder: shifting toward a developmental framework. Child Adolesc Psychiatr Clin N Am (2012) 21:573-91. doi:10.1016/j.chc.2012.05.004
    • (2012) Child Adolesc Psychiatr Clin N Am , vol.21 , pp. 573-591
    • Carrion, V.G.1    Kletter, H.2
  • 19
    • 84873851437 scopus 로고    scopus 로고
    • Implications of memory modulation for post-traumatic stress and fear disorders
    • doi:10.1038/nn.3296
    • Parsons RG, Ressler KJ. Implications of memory modulation for post-traumatic stress and fear disorders. Nat Neurosci (2013) 16:146-53. doi:10.1038/nn.3296
    • (2013) Nat Neurosci , vol.16 , pp. 146-153
    • Parsons, R.G.1    Ressler, K.J.2
  • 20
    • 84883766047 scopus 로고    scopus 로고
    • Hippocampal neurogenesis and forgetting
    • doi:10.1016/j.tins.2013.05.002
    • Frankland PW, Kohler S, Josselyn SA. Hippocampal neurogenesis and forgetting. Trends Neurosci (2013) 36:497-503. doi:10.1016/j.tins.2013.05.002
    • (2013) Trends Neurosci , vol.36 , pp. 497-503
    • Frankland, P.W.1    Kohler, S.2    Josselyn, S.A.3
  • 21
    • 78149476696 scopus 로고    scopus 로고
    • Removing brakes on adult brain plasticity: from molecular to behavioral interventions
    • doi:10.1523/JNEUROSCI.4812-10.2010
    • Bavelier D, Levi DM, Li RW, Dan Y, Hensch TK. Removing brakes on adult brain plasticity: from molecular to behavioral interventions. J Neurosci (2010) 30:14964-71. doi:10.1523/JNEUROSCI.4812-10.2010
    • (2010) J Neurosci , vol.30 , pp. 14964-14971
    • Bavelier, D.1    Levi, D.M.2    Li, R.W.3    Dan, Y.4    Hensch, T.K.5
  • 22
    • 0037044829 scopus 로고    scopus 로고
    • Reactivation of ocular dominance plasticity in the adult visual cortex
    • doi:10.1126/science.1072699
    • Pizzorusso T, Medini P, Berardi N, Chierzi S, Fawcett JW, Maffei L. Reactivation of ocular dominance plasticity in the adult visual cortex. Science (2002) 298:1248-51. doi:10.1126/science.1072699
    • (2002) Science , vol.298 , pp. 1248-1251
    • Pizzorusso, T.1    Medini, P.2    Berardi, N.3    Chierzi, S.4    Fawcett, J.W.5    Maffei, L.6
  • 23
    • 25844467735 scopus 로고    scopus 로고
    • Experience-driven plasticity of visual cortex limited by myelin and Nogo receptor
    • doi:10.1126/science.1114362
    • McGee AW, Yang Y, Fischer QS, Daw NW, Strittmatter SM. Experience-driven plasticity of visual cortex limited by myelin and Nogo receptor. Science (2005) 309:2222-6. doi:10.1126/science.1114362
    • (2005) Science , vol.309 , pp. 2222-2226
    • McGee, A.W.1    Yang, Y.2    Fischer, Q.S.3    Daw, N.W.4    Strittmatter, S.M.5
  • 24
    • 33749007674 scopus 로고    scopus 로고
    • PirB restricts ocular-dominance plasticity in visual cortex
    • doi:10.1126/science.1128232
    • Syken J, Grandpre T, Kanold PO, Shatz CJ. PirB restricts ocular-dominance plasticity in visual cortex. Science (2006) 313:1795-800. doi:10.1126/science.1128232
    • (2006) Science , vol.313 , pp. 1795-1800
    • Syken, J.1    Grandpre, T.2    Kanold, P.O.3    Shatz, C.J.4
  • 25
    • 78649442213 scopus 로고    scopus 로고
    • Lynx1, a cholinergic brake, limits plasticity in adult visual cortex
    • doi:10.1126/science.1195320
    • Morishita H, Miwa JM, Heintz N, Hensch TK. Lynx1, a cholinergic brake, limits plasticity in adult visual cortex. Science (2010) 330:1238-40. doi:10.1126/science.1195320
    • (2010) Science , vol.330 , pp. 1238-1240
    • Morishita, H.1    Miwa, J.M.2    Heintz, N.3    Hensch, T.K.4
  • 26
    • 80053916181 scopus 로고    scopus 로고
    • Extracellular matrix and perineuronal nets in CNS repair
    • doi:10.1002/dneu.20974
    • Kwok JC, Dick G, Wang D, Fawcett JW. Extracellular matrix and perineuronal nets in CNS repair. Dev Neurobiol (2011) 71:1073-89. doi:10.1002/dneu.20974
    • (2011) Dev Neurobiol , vol.71 , pp. 1073-1089
    • Kwok, J.C.1    Dick, G.2    Wang, D.3    Fawcett, J.W.4
  • 27
    • 77955148070 scopus 로고    scopus 로고
    • Animals lacking link protein have attenuated perineuronal nets and persistent plasticity
    • doi:10.1093/brain/awq145
    • Carulli D, Pizzorusso T, Kwok JC, Putignano E, Poli A, Forostyak S, et al. Animals lacking link protein have attenuated perineuronal nets and persistent plasticity. Brain (2010) 133:2331-47. doi:10.1093/brain/awq145
    • (2010) Brain , vol.133 , pp. 2331-2347
    • Carulli, D.1    Pizzorusso, T.2    Kwok, J.C.3    Putignano, E.4    Poli, A.5    Forostyak, S.6
  • 28
    • 33744781051 scopus 로고    scopus 로고
    • Structural and functional recovery from early monocular deprivation in adult rats
    • doi:10.1073/pnas.0602657103
    • Pizzorusso T, Medini P, Landi S, Baldini S, Berardi N, Maffei L. Structural and functional recovery from early monocular deprivation in adult rats. Proc Natl Acad Sci U S A (2006) 103:8517-22. doi:10.1073/pnas.0602657103
    • (2006) Proc Natl Acad Sci U S A , vol.103 , pp. 8517-8522
    • Pizzorusso, T.1    Medini, P.2    Landi, S.3    Baldini, S.4    Berardi, N.5    Maffei, L.6
  • 29
    • 84863492175 scopus 로고    scopus 로고
    • Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex
    • doi:10.1523/JNEUROSCI.0394-12.2012
    • Beurdeley M, Spatazza J, Lee HH, Sugiyama S, Bernard C, Di Nardo AA, et al. Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex. J Neurosci (2012) 32:9429-37. doi:10.1523/JNEUROSCI.0394-12.2012
    • (2012) J Neurosci , vol.32 , pp. 9429-9437
    • Beurdeley, M.1    Spatazza, J.2    Lee, H.H.3    Sugiyama, S.4    Bernard, C.5    Di Nardo, A.A.6
  • 30
    • 84857641919 scopus 로고    scopus 로고
    • Persistent cortical plasticity by upregulation of chondroitin 6-sulfation
    • doi:10.1038/nn.3023
    • Miyata S, Komatsu Y, Yoshimura Y, Taya C, Kitagawa H. Persistent cortical plasticity by upregulation of chondroitin 6-sulfation. Nat Neurosci (2012) 15(414-422):S411-2. doi:10.1038/nn.3023
    • (2012) Nat Neurosci , vol.15 , Issue.414-422
    • Miyata, S.1    Komatsu, Y.2    Yoshimura, Y.3    Taya, C.4    Kitagawa, H.5
  • 31
    • 84879793351 scopus 로고    scopus 로고
    • Choroid-plexus-derived otx2 homeoprotein constrains adult cortical plasticity
    • doi:10.1016/j.celrep.2013.05.014
    • Spatazza J, Lee HH, Di Nardo AA, Tibaldi L, Joliot A, Hensch TK, et al. Choroid-plexus-derived otx2 homeoprotein constrains adult cortical plasticity. Cell Reports (2013) 3:1815-23. doi:10.1016/j.celrep.2013.05.014
    • (2013) Cell Reports , vol.3 , pp. 1815-1823
    • Spatazza, J.1    Lee, H.H.2    Di Nardo, A.A.3    Tibaldi, L.4    Joliot, A.5    Hensch, T.K.6
  • 32
    • 48449089927 scopus 로고    scopus 로고
    • Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity
    • doi:10.1016/j.cell.2008.05.054
    • Sugiyama S, Di Nardo AA, Aizawa S, Matsuo I, Volovitch M, Prochiantz A, et al. Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity. Cell (2008) 134:508-20. doi:10.1016/j.cell.2008.05.054
    • (2008) Cell , vol.134 , pp. 508-520
    • Sugiyama, S.1    Di Nardo, A.A.2    Aizawa, S.3    Matsuo, I.4    Volovitch, M.5    Prochiantz, A.6
  • 33
    • 76149138048 scopus 로고    scopus 로고
    • Extracellular matrix-glial abnormalities in the amygdala and entorhinal cortex of subjects diagnosed with schizophrenia
    • doi:10.1001/archgenpsychiatry.2009.196
    • Pantazopoulos H, Woo TU, Lim MP, Lange N, Berretta S. Extracellular matrix-glial abnormalities in the amygdala and entorhinal cortex of subjects diagnosed with schizophrenia. Arch Gen Psychiatry (2010) 67:155-66. doi:10.1001/archgenpsychiatry.2009.196
    • (2010) Arch Gen Psychiatry , vol.67 , pp. 155-166
    • Pantazopoulos, H.1    Woo, T.U.2    Lim, M.P.3    Lange, N.4    Berretta, S.5
  • 34
    • 84874511171 scopus 로고    scopus 로고
    • Early-life insults impair parvalbumin interneurons via oxidative stress: reversal by N-acetylcysteine
    • doi:10.1016/j.biopsych.2012.09.020
    • Cabungcal JH, Steullet P, Kraftsik R, Cuenod M, Do KQ. Early-life insults impair parvalbumin interneurons via oxidative stress: reversal by N-acetylcysteine. Biol Psychiatry (2013) 73:574-82. doi:10.1016/j.biopsych.2012.09.020
    • (2013) Biol Psychiatry , vol.73 , pp. 574-582
    • Cabungcal, J.H.1    Steullet, P.2    Kraftsik, R.3    Cuenod, M.4    Do, K.Q.5
  • 35
  • 36
    • 84859899331 scopus 로고    scopus 로고
    • Myelin associated inhibitors: a link between injury-induced and experience-dependent plasticity
    • doi:10.1016/j.expneurol.2011.06.006
    • Akbik F, Cafferty WB, Strittmatter SM. Myelin associated inhibitors: a link between injury-induced and experience-dependent plasticity. Exp Neurol (2012) 235:43-52. doi:10.1016/j.expneurol.2011.06.006
    • (2012) Exp Neurol , vol.235 , pp. 43-52
    • Akbik, F.1    Cafferty, W.B.2    Strittmatter, S.M.3
  • 37
    • 84876450980 scopus 로고    scopus 로고
    • Anatomical plasticity of adult brain is titrated by Nogo Receptor 1
    • doi:10.1016/j.neuron.2012.12.027
    • Akbik FV, Bhagat SM, Patel PR, Cafferty WB, Strittmatter SM. Anatomical plasticity of adult brain is titrated by Nogo Receptor 1. Neuron (2013) 77:859-66. doi:10.1016/j.neuron.2012.12.027
    • (2013) Neuron , vol.77 , pp. 859-866
    • Akbik, F.V.1    Bhagat, S.M.2    Patel, P.R.3    Cafferty, W.B.4    Strittmatter, S.M.5
  • 38
    • 84857794142 scopus 로고    scopus 로고
    • Opposite effects of fear conditioning and extinction on dendritic spine remodelling
    • doi:10.1038/nature10792
    • Lai CS, Franke TF, Gan WB. Opposite effects of fear conditioning and extinction on dendritic spine remodelling. Nature (2012) 483:87-91. doi:10.1038/nature10792
    • (2012) Nature , vol.483 , pp. 87-91
    • Lai, C.S.1    Franke, T.F.2    Gan, W.B.3
  • 39
    • 0033136270 scopus 로고    scopus 로고
    • lynx1, an endogenous toxin-like modulator of nicotinic acetylcholine receptors in the mammalian CNS
    • doi:10.1016/S0896-6273(00)80757-6
    • Miwa JM, Ibanez-Tallon I, Crabtree GW, Sanchez R, Sali A, Role LW, et al. lynx1, an endogenous toxin-like modulator of nicotinic acetylcholine receptors in the mammalian CNS. Neuron (1999) 23:105-14. doi:10.1016/S0896-6273(00)80757-6
    • (1999) Neuron , vol.23 , pp. 105-114
    • Miwa, J.M.1    Ibanez-Tallon, I.2    Crabtree, G.W.3    Sanchez, R.4    Sali, A.5    Role, L.W.6
  • 40
    • 0022619482 scopus 로고
    • Modulation of visual cortical plasticity by acetylcholine and noradrenaline
    • doi:10.1038/320172a0
    • Bear MF, Singer W. Modulation of visual cortical plasticity by acetylcholine and noradrenaline. Nature (1986) 320:172-6. doi:10.1038/320172a0
    • (1986) Nature , vol.320 , pp. 172-176
    • Bear, M.F.1    Singer, W.2
  • 41
    • 80054993342 scopus 로고    scopus 로고
    • Spatio-temporal transcriptome of the human brain
    • doi:10.1038/nature10523
    • Kang HJ, Kawasawa YI, Cheng F, Zhu Y, Xu X, Li M, et al. Spatio-temporal transcriptome of the human brain. Nature (2011) 478:483-9. doi:10.1038/nature10523
    • (2011) Nature , vol.478 , pp. 483-489
    • Kang, H.J.1    Kawasawa, Y.I.2    Cheng, F.3    Zhu, Y.4    Xu, X.5    Li, M.6
  • 42
    • 33748081791 scopus 로고    scopus 로고
    • The prototoxin lynx1 acts on nicotinic acetylcholine receptors to balance neuronal activity and survival in vivo
    • doi:10.1016/j.neuron.2006.07.025
    • Miwa JM, Stevens TR, King SL, Caldarone BJ, Ibanez-Tallon I, Xiao C, et al. The prototoxin lynx1 acts on nicotinic acetylcholine receptors to balance neuronal activity and survival in vivo. Neuron (2006) 51:587-600. doi:10.1016/j.neuron.2006.07.025
    • (2006) Neuron , vol.51 , pp. 587-600
    • Miwa, J.M.1    Stevens, T.R.2    King, S.L.3    Caldarone, B.J.4    Ibanez-Tallon, I.5    Xiao, C.6
  • 44
    • 79551624514 scopus 로고    scopus 로고
    • Selective early-acquired fear memories undergo temporary suppression during adolescence
    • doi:10.1073/pnas.1012975108
    • Pattwell SS, Bath KG, Casey BJ, Ninan I, Lee FS. Selective early-acquired fear memories undergo temporary suppression during adolescence. Proc Natl Acad Sci USA (2011) 108:1182-7. doi:10.1073/pnas.1012975108
    • (2011) Proc Natl Acad Sci USA , vol.108 , pp. 1182-1187
    • Pattwell, S.S.1    Bath, K.G.2    Casey, B.J.3    Ninan, I.4    Lee, F.S.5
  • 45
    • 73749083530 scopus 로고    scopus 로고
    • Nicotine and extinction of fear conditioning
    • doi:10.1016/j.neuroscience.2009.11.022
    • Elias GA, Gulick D, Wilkinson DS, Gould TJ. Nicotine and extinction of fear conditioning. Neuroscience (2010) 165:1063-73. doi:10.1016/j.neuroscience.2009.11.022
    • (2010) Neuroscience , vol.165 , pp. 1063-1073
    • Elias, G.A.1    Gulick, D.2    Wilkinson, D.S.3    Gould, T.J.4
  • 46
    • 33847174581 scopus 로고    scopus 로고
    • A randomized controlled trial of the effect of D-cycloserine on extinction and fear conditioning in humans
    • doi:10.1016/j.brat.2006.07.005
    • Guastella AJ, Lovibond PF, Dadds MR, Mitchell P, Richardson R. A randomized controlled trial of the effect of D-cycloserine on extinction and fear conditioning in humans. Behav Res Ther (2007) 45:663-72. doi:10.1016/j.brat.2006.07.005
    • (2007) Behav Res Ther , vol.45 , pp. 663-672
    • Guastella, A.J.1    Lovibond, P.F.2    Dadds, M.R.3    Mitchell, P.4    Richardson, R.5
  • 47
    • 78049428115 scopus 로고    scopus 로고
    • d-serine enhances extinction of auditory cued fear conditioning via ERK1/2 phosphorylation in mice
    • doi:10.1016/j.pnpbp.2010.04.013
    • Matsuda S, Matsuzawa D, Nakazawa K, Sutoh C, Ohtsuka H, Ishii D, et al. d-serine enhances extinction of auditory cued fear conditioning via ERK1/2 phosphorylation in mice. Prog Neuropsychopharmacol Biol Psychiatry (2010) 34:895-902. doi:10.1016/j.pnpbp.2010.04.013
    • (2010) Prog Neuropsychopharmacol Biol Psychiatry , vol.34 , pp. 895-902
    • Matsuda, S.1    Matsuzawa, D.2    Nakazawa, K.3    Sutoh, C.4    Ohtsuka, H.5    Ishii, D.6
  • 48
    • 33846527318 scopus 로고    scopus 로고
    • Clinical perspectives on the combination of D-cycloserine and cognitive-behavioral therapy for the treatment of anxiety disorders
    • Otto MW, Basden SL, Leyro TM, McHugh RK, Hofmann SG. Clinical perspectives on the combination of D-cycloserine and cognitive-behavioral therapy for the treatment of anxiety disorders. CNS Spectr (2007) 12(51-56):59-61.
    • (2007) CNS Spectr , vol.12 , Issue.51-56 , pp. 59-61
    • Otto, M.W.1    Basden, S.L.2    Leyro, T.M.3    McHugh, R.K.4    Hofmann, S.G.5
  • 49
    • 33947594122 scopus 로고    scopus 로고
    • Effects of D-cycloserine on extinction of learned fear to an olfactory cue
    • doi:10.1016/j.nlm.2006.12.010
    • Weber M, Hart J, Richardson R. Effects of D-cycloserine on extinction of learned fear to an olfactory cue. Neurobiol Learn Mem (2007) 87:476-82. doi:10.1016/j.nlm.2006.12.010
    • (2007) Neurobiol Learn Mem , vol.87 , pp. 476-482
    • Weber, M.1    Hart, J.2    Richardson, R.3
  • 50
    • 42349094651 scopus 로고    scopus 로고
    • The antidepressant fluoxetine restores plasticity in the adult visual cortex
    • doi:10.1126/science.1150516
    • Maya Vetencourt JF, Sale A, Viegi A, Baroncelli L, De Pasquale R, O'Leary OF, et al. The antidepressant fluoxetine restores plasticity in the adult visual cortex. Science (2008) 320:385-8. doi:10.1126/science.1150516
    • (2008) Science , vol.320 , pp. 385-388
    • Maya Vetencourt, J.F.1    Sale, A.2    Viegi, A.3    Baroncelli, L.4    De Pasquale, R.5    O'Leary, O.F.6
  • 51
    • 84455171593 scopus 로고    scopus 로고
    • Fear erasure in mice requires synergy between antidepressant drugs and extinction training
    • doi:10.1126/science.1214592
    • Karpova NN, Pickenhagen A, Lindholm J, Tiraboschi E, Kulesskaya N, Agustsdottir A, et al. Fear erasure in mice requires synergy between antidepressant drugs and extinction training. Science (2011) 334:1731-4. doi:10.1126/science.1214592
    • (2011) Science , vol.334 , pp. 1731-1734
    • Karpova, N.N.1    Pickenhagen, A.2    Lindholm, J.3    Tiraboschi, E.4    Kulesskaya, N.5    Agustsdottir, A.6
  • 52
    • 77952352765 scopus 로고    scopus 로고
    • Reversal of hippocampal neuronal maturation by serotonergic antidepressants
    • doi:10.1073/pnas.0912690107
    • Kobayashi K, Ikeda Y, Sakai A, Yamasaki N, Haneda E, Miyakawa T, et al. Reversal of hippocampal neuronal maturation by serotonergic antidepressants. Proc Natl Acad Sci U S A (2010) 107(18):8434-9. doi:10.1073/pnas.0912690107
    • (2010) Proc Natl Acad Sci U S A , vol.107 , Issue.18 , pp. 8434-8439
    • Kobayashi, K.1    Ikeda, Y.2    Sakai, A.3    Yamasaki, N.4    Haneda, E.5    Miyakawa, T.6
  • 53
    • 84865001683 scopus 로고    scopus 로고
    • Long-lasting hippocampal synaptic protein loss in a mouse model of posttraumatic stress disorder
    • doi:10.1371/journal.pone.0042603
    • Herrmann L, Ionescu IA, Henes K, Golub Y, Wang NX, Buell DR, et al. Long-lasting hippocampal synaptic protein loss in a mouse model of posttraumatic stress disorder. PLoS One (2012) 7:e42603. doi:10.1371/journal.pone.0042603
    • (2012) PLoS One , vol.7
    • Herrmann, L.1    Ionescu, I.A.2    Henes, K.3    Golub, Y.4    Wang, N.X.5    Buell, D.R.6
  • 54
    • 80053585289 scopus 로고    scopus 로고
    • Acetylcholinesterase inhibitors rapidly activate Trk neurotrophin receptors in the mouse hippocampus
    • doi:10.1016/j.neuropharm.2011.07.033
    • Autio H, Matlik K, Rantamaki T, Lindemann L, Hoener MC, Chao M, et al. Acetylcholinesterase inhibitors rapidly activate Trk neurotrophin receptors in the mouse hippocampus. Neuropharmacology (2011) 61:1291-6. doi:10.1016/j.neuropharm.2011.07.033
    • (2011) Neuropharmacology , vol.61 , pp. 1291-1296
    • Autio, H.1    Matlik, K.2    Rantamaki, T.3    Lindemann, L.4    Hoener, M.C.5    Chao, M.6
  • 55
    • 33847150936 scopus 로고    scopus 로고
    • Developmental downregulation of histone posttranslational modifications regulates visual cortical plasticity
    • doi:10.1016/j.neuron.2007.02.007
    • Putignano E, Lonetti G, Cancedda L, Ratto G, Costa M, Maffei L, et al. Developmental downregulation of histone posttranslational modifications regulates visual cortical plasticity. Neuron (2007) 53:747-59. doi:10.1016/j.neuron.2007.02.007
    • (2007) Neuron , vol.53 , pp. 747-759
    • Putignano, E.1    Lonetti, G.2    Cancedda, L.3    Ratto, G.4    Costa, M.5    Maffei, L.6
  • 56
    • 77953737800 scopus 로고    scopus 로고
    • Epigenetic treatments of adult rats promote recovery from visual acuity deficits induced by long-term monocular deprivation
    • doi:10.1111/j.1460-9568.2010.07261.x
    • Silingardi D, Scali M, Belluomini G, Pizzorusso T. Epigenetic treatments of adult rats promote recovery from visual acuity deficits induced by long-term monocular deprivation. Eur J Neurosci (2010) 31:2185-92. doi:10.1111/j.1460-9568.2010.07261.x
    • (2010) Eur J Neurosci , vol.31 , pp. 2185-2192
    • Silingardi, D.1    Scali, M.2    Belluomini, G.3    Pizzorusso, T.4
  • 57
    • 77950867183 scopus 로고    scopus 로고
    • Epigenetic regulation of oligodendrocyte identity
    • doi:10.1016/j.tins.2010.01.007
    • Liu J, Casaccia P. Epigenetic regulation of oligodendrocyte identity. Trends Neurosci (2010) 33:193-201. doi:10.1016/j.tins.2010.01.007
    • (2010) Trends Neurosci , vol.33 , pp. 193-201
    • Liu, J.1    Casaccia, P.2
  • 58
    • 22344446199 scopus 로고    scopus 로고
    • Histone modifications affect timing of oligodendrocyte progenitor differentiation in the developing rat brain
    • doi:10.1083/jcb.200412101
    • Shen S, Li J, Casaccia-Bonnefil P. Histone modifications affect timing of oligodendrocyte progenitor differentiation in the developing rat brain. J Cell Biol (2005) 169:577-89. doi:10.1083/jcb.200412101
    • (2005) J Cell Biol , vol.169 , pp. 577-589
    • Shen, S.1    Li, J.2    Casaccia-Bonnefil, P.3
  • 59
    • 50249167673 scopus 로고    scopus 로고
    • Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency
    • doi:10.1038/nn.2172
    • Shen S, Sandoval J, Swiss VA, Li J, Dupree J, Franklin RJ, et al. Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency. Nat Neurosci (2008) 11:1024-34. doi:10.1038/nn.2172
    • (2008) Nat Neurosci , vol.11 , pp. 1024-1034
    • Shen, S.1    Sandoval, J.2    Swiss, V.A.3    Li, J.4    Dupree, J.5    Franklin, R.J.6
  • 60
    • 38649140454 scopus 로고    scopus 로고
    • The histone deacetylase inhibitor valproic acid enhances acquisition, extinction, and reconsolidation of conditioned fear
    • doi:10.1101/lm.801108
    • Bredy TW, Barad M. The histone deacetylase inhibitor valproic acid enhances acquisition, extinction, and reconsolidation of conditioned fear. Learn Mem (2008) 15:39-45. doi:10.1101/lm.801108
    • (2008) Learn Mem , vol.15 , pp. 39-45
    • Bredy, T.W.1    Barad, M.2
  • 61
    • 34247224239 scopus 로고    scopus 로고
    • Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear
    • doi:10.1101/lm.500907
    • Bredy TW, Wu H, Crego C, Zellhoefer J, Sun YE, Barad M. Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear. Learn Mem (2007) 14:268-76. doi:10.1101/lm.500907
    • (2007) Learn Mem , vol.14 , pp. 268-276
    • Bredy, T.W.1    Wu, H.2    Crego, C.3    Zellhoefer, J.4    Sun, Y.E.5    Barad, M.6
  • 62
    • 84861187647 scopus 로고    scopus 로고
    • Histone acetylation rescues contextual fear conditioning in nNOS KO mice and accelerates extinction of cued fear conditioning in wild type mice
    • doi:10.1016/j.nlm.2012.03.005
    • Itzhak Y, Anderson KL, Kelley JB, Petkov M. Histone acetylation rescues contextual fear conditioning in nNOS KO mice and accelerates extinction of cued fear conditioning in wild type mice. Neurobiol Learn Mem (2012) 97:409-17. doi:10.1016/j.nlm.2012.03.005
    • (2012) Neurobiol Learn Mem , vol.97 , pp. 409-417
    • Itzhak, Y.1    Anderson, K.L.2    Kelley, J.B.3    Petkov, M.4
  • 63
    • 35748972690 scopus 로고    scopus 로고
    • Systemic or intrahippocampal delivery of histone deacetylase inhibitors facilitates fear extinction
    • doi:10.1037/0735-7044.121.5.1125
    • Lattal KM, Barrett RM, Wood MA. Systemic or intrahippocampal delivery of histone deacetylase inhibitors facilitates fear extinction. Behav Neurosci (2007) 121:1125-31. doi:10.1037/0735-7044.121.5.1125
    • (2007) Behav Neurosci , vol.121 , pp. 1125-1131
    • Lattal, K.M.1    Barrett, R.M.2    Wood, M.A.3
  • 64
    • 84861187305 scopus 로고    scopus 로고
    • Increasing histone acetylation in the hippocampus-infralimbic network enhances fear extinction
    • doi:10.1016/j.biopsych.2011.12.012
    • Stafford JM, Raybuck JD, Ryabinin AE, Lattal KM. Increasing histone acetylation in the hippocampus-infralimbic network enhances fear extinction. Biol Psychiatry (2012) 72:25-33. doi:10.1016/j.biopsych.2011.12.012
    • (2012) Biol Psychiatry , vol.72 , pp. 25-33
    • Stafford, J.M.1    Raybuck, J.D.2    Ryabinin, A.E.3    Lattal, K.M.4
  • 65
    • 34249667112 scopus 로고    scopus 로고
    • Environmental enrichment in adulthood promotes amblyopia recovery through a reduction of intracortical inhibition
    • doi:10.1038/nn1899
    • Sale A, Maya Vetencourt JF, Medini P, Cenni MC, Baroncelli L, De Pasquale R, et al. Environmental enrichment in adulthood promotes amblyopia recovery through a reduction of intracortical inhibition. Nat Neurosci (2007) 10:679-81. doi:10.1038/nn1899
    • (2007) Nat Neurosci , vol.10 , pp. 679-681
    • Sale, A.1    Maya Vetencourt, J.F.2    Medini, P.3    Cenni, M.C.4    Baroncelli, L.5    De Pasquale, R.6
  • 66
    • 34548321217 scopus 로고    scopus 로고
    • Experience-dependent recovery of vision following chronic deprivation amblyopia
    • doi:10.1038/nn1965
    • He HY, Ray B, Dennis K, Quinlan EM. Experience-dependent recovery of vision following chronic deprivation amblyopia. Nat Neurosci (2007) 10:1134-6. doi:10.1038/nn1965
    • (2007) Nat Neurosci , vol.10 , pp. 1134-1136
    • He, H.Y.1    Ray, B.2    Dennis, K.3    Quinlan, E.M.4
  • 67
    • 58149252228 scopus 로고    scopus 로고
    • Improving the performance of the amblyopic visual system
    • doi:10.1098/rstb.2008.0203
    • Levi DM, Li RW. Improving the performance of the amblyopic visual system. Philos Trans R Soc Lond B Biol Sci (2009) 364:399-407. doi:10.1098/rstb.2008.0203
    • (2009) Philos Trans R Soc Lond B Biol Sci , vol.364 , pp. 399-407
    • Levi, D.M.1    Li, R.W.2
  • 68
    • 70349913676 scopus 로고    scopus 로고
    • Making perceptual learning practical to improve visual functions
    • doi:10.1016/j.visres.2009.06.005
    • Polat U. Making perceptual learning practical to improve visual functions. Vision Res (2009) 49:2566-73. doi:10.1016/j.visres.2009.06.005
    • (2009) Vision Res , vol.49 , pp. 2566-2573
    • Polat, U.1
  • 69
    • 33846231797 scopus 로고    scopus 로고
    • Involuntary awareness and implicit priming: role of retrieval context
    • doi:10.2466/PMS.103.6.344-353
    • Zhou R, Hu S, Sun X, Huang J. Involuntary awareness and implicit priming: role of retrieval context. Percept Mot Skills (2006) 103:344-53. doi:10.2466/PMS.103.6.344-353
    • (2006) Percept Mot Skills , vol.103 , pp. 344-353
    • Zhou, R.1    Hu, S.2    Sun, X.3    Huang, J.4
  • 70
    • 84874886038 scopus 로고    scopus 로고
    • The effect of video game training on the vision of adults with bilateral deprivation amblyopia
    • doi:10.1163/18784763-00002391
    • Jeon ST, Maurer D, Lewis TL. The effect of video game training on the vision of adults with bilateral deprivation amblyopia. Seeing Perceiving (2012) 25:493-520. doi:10.1163/18784763-00002391
    • (2012) Seeing Perceiving , vol.25 , pp. 493-520
    • Jeon, S.T.1    Maurer, D.2    Lewis, T.L.3
  • 71
    • 80052312967 scopus 로고    scopus 로고
    • Video-game play induces plasticity in the visual system of adults with amblyopia
    • doi:10.1371/journal.pbio.1001135
    • Li RW, Ngo C, Nguyen J, Levi DM. Video-game play induces plasticity in the visual system of adults with amblyopia. PLoS Biol (2011) 9:e1001135. doi:10.1371/journal.pbio.1001135
    • (2011) PLoS Biol , vol.9
    • Li, R.W.1    Ngo, C.2    Nguyen, J.3    Levi, D.M.4
  • 72
    • 78449285958 scopus 로고    scopus 로고
    • Calcium-permeable AMPA receptor dynamics mediate fear memory erasure
    • doi:10.1126/science.1195298
    • Clem RL, Huganir RL. Calcium-permeable AMPA receptor dynamics mediate fear memory erasure. Science (2010) 330:1108-12. doi:10.1126/science.1195298
    • (2010) Science , vol.330 , pp. 1108-1112
    • Clem, R.L.1    Huganir, R.L.2
  • 73
    • 66149153122 scopus 로고    scopus 로고
    • Extinction-reconsolidation boundaries: key to persistent attenuation of fear memories
    • doi:10.1126/science.1167975
    • Monfils MH, Cowansage KK, Klann E, LeDoux JE. Extinction-reconsolidation boundaries: key to persistent attenuation of fear memories. Science (2009) 324:951-5. doi:10.1126/science.1167975
    • (2009) Science , vol.324 , pp. 951-955
    • Monfils, M.H.1    Cowansage, K.K.2    Klann, E.3    LeDoux, J.E.4
  • 74
    • 73849133254 scopus 로고    scopus 로고
    • Preventing the return of fear in humans using reconsolidation update mechanisms
    • doi:10.1038/nature08637
    • Schiller D, Monfils MH, Raio CM, Johnson DC, Ledoux JE, Phelps EA. Preventing the return of fear in humans using reconsolidation update mechanisms. Nature (2010) 463:49-53. doi:10.1038/nature08637
    • (2010) Nature , vol.463 , pp. 49-53
    • Schiller, D.1    Monfils, M.H.2    Raio, C.M.3    Johnson, D.C.4    Ledoux, J.E.5    Phelps, E.A.6
  • 75
    • 84866452626 scopus 로고    scopus 로고
    • Disruption of reconsolidation erases a fear memory trace in the human amygdala
    • doi:10.1126/science.1223006
    • Agren T, Engman J, Frick A, Bjorkstrand J, Larsson EM, Furmark T, et al. Disruption of reconsolidation erases a fear memory trace in the human amygdala. Science (2012) 337:1550-2. doi:10.1126/science.1223006
    • (2012) Science , vol.337 , pp. 1550-1552
    • Agren, T.1    Engman, J.2    Frick, A.3    Bjorkstrand, J.4    Larsson, E.M.5    Furmark, T.6
  • 76
    • 0034680134 scopus 로고    scopus 로고
    • Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval
    • doi:10.1038/35021052
    • Nader K, Schafe GE, Le Doux JE. Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature (2000) 406:722-6. doi:10.1038/35021052
    • (2000) Nature , vol.406 , pp. 722-726
    • Nader, K.1    Schafe, G.E.2    Le Doux, J.E.3
  • 77
    • 38649111691 scopus 로고    scopus 로고
    • Focal brain damage protects against post-traumatic stress disorder in combat veterans
    • doi:10.1038/nn2032
    • Koenigs M, Huey ED, Raymont V, Cheon B, Solomon J, Wassermann EM, et al. Focal brain damage protects against post-traumatic stress disorder in combat veterans. Nat Neurosci (2008) 11:232-7. doi:10.1038/nn2032
    • (2008) Nat Neurosci , vol.11 , pp. 232-237
    • Koenigs, M.1    Huey, E.D.2    Raymont, V.3    Cheon, B.4    Solomon, J.5    Wassermann, E.M.6
  • 78
    • 78149481093 scopus 로고    scopus 로고
    • Erasing fear memories with extinction training
    • doi:10.1523/JNEUROSCI.4268-10.2010
    • Quirk GJ, Pare D, Richardson R, Herry C, Monfils MH, Schiller D, et al. Erasing fear memories with extinction training. J Neurosci (2010) 30:14993-7. doi:10.1523/JNEUROSCI.4268-10.2010
    • (2010) J Neurosci , vol.30 , pp. 14993-14997
    • Quirk, G.J.1    Pare, D.2    Richardson, R.3    Herry, C.4    Monfils, M.H.5    Schiller, D.6
  • 79
    • 69749101049 scopus 로고    scopus 로고
    • Fear extinction across development: the involvement of the medial prefrontal cortex as assessed by temporary inactivation and immunohistochemistry
    • doi:10.1523/JNEUROSCI.0596-09.2009
    • Kim JH, Hamlin AS, Richardson R. Fear extinction across development: the involvement of the medial prefrontal cortex as assessed by temporary inactivation and immunohistochemistry. J Neurosci (2009) 29:10802-8. doi:10.1523/JNEUROSCI.0596-09.2009
    • (2009) J Neurosci , vol.29 , pp. 10802-10808
    • Kim, J.H.1    Hamlin, A.S.2    Richardson, R.3
  • 80
    • 84859627879 scopus 로고    scopus 로고
    • A memory retrieval-extinction procedure to prevent drug craving and relapse
    • doi:10.1126/science.1215070
    • Xue YX, Luo YX, Wu P, Shi HS, Xue LF, Chen C, et al. A memory retrieval-extinction procedure to prevent drug craving and relapse. Science (2012) 336:241-5. doi:10.1126/science.1215070
    • (2012) Science , vol.336 , pp. 241-245
    • Xue, Y.X.1    Luo, Y.X.2    Wu, P.3    Shi, H.S.4    Xue, L.F.5    Chen, C.6
  • 81
    • 34548585044 scopus 로고    scopus 로고
    • The IkappaB kinase regulates chromatin structure during reconsolidation of conditioned fear memories
    • doi:10.1016/j.neuron.2007.07.039
    • Lubin FD, Sweatt JD. The IkappaB kinase regulates chromatin structure during reconsolidation of conditioned fear memories. Neuron (2007) 55:942-57. doi:10.1016/j.neuron.2007.07.039
    • (2007) Neuron , vol.55 , pp. 942-957
    • Lubin, F.D.1    Sweatt, J.D.2
  • 82
    • 79956314152 scopus 로고    scopus 로고
    • The activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) is required for reconsolidation of a Pavlovian fear memory
    • doi:10.1523/JNEUROSCI.1120-11.2011
    • Maddox SA, Schafe GE. The activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) is required for reconsolidation of a Pavlovian fear memory. J Neurosci (2011) 31:7073-82. doi:10.1523/JNEUROSCI.1120-11.2011
    • (2011) J Neurosci , vol.31 , pp. 7073-7082
    • Maddox, S.A.1    Schafe, G.E.2
  • 84
    • 0038174616 scopus 로고    scopus 로고
    • Memory retrieval after contextual fear conditioning induces c-Fos and JunB expression in CA1 hippocampus
    • doi:10.1034/j.1601-183X.2003.00001.x
    • Strekalova T, Zorner B, Zacher C, Sadovska G, Herdegen T, Gass P. Memory retrieval after contextual fear conditioning induces c-Fos and JunB expression in CA1 hippocampus. Genes Brain Behav (2003) 2:3-10. doi:10.1034/j.1601-183X.2003.00001.x
    • (2003) Genes Brain Behav , vol.2 , pp. 3-10
    • Strekalova, T.1    Zorner, B.2    Zacher, C.3    Sadovska, G.4    Herdegen, T.5    Gass, P.6
  • 85
    • 84869094967 scopus 로고    scopus 로고
    • Epigenetic mechanisms in learned fear: implications for PTSD
    • doi:10.1038/npp.2012.79
    • Zovkic IB, Sweatt JD. Epigenetic mechanisms in learned fear: implications for PTSD. Neuropsychopharmacology (2013) 38:77-93. doi:10.1038/npp.2012.79
    • (2013) Neuropsychopharmacology , vol.38 , pp. 77-93
    • Zovkic, I.B.1    Sweatt, J.D.2


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