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Translational Regulation of Synaptic Plasticity

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Multidisciplinary Tools for Investigating Synaptic Plasticity

Part of the book series: Neuromethods ((NM,volume 81))

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Abstract

Synaptic plasticity defines the process by which synapses, the connections between neurons, can be modified in response to activity. Plasticity can be either positive or negative, with strengthening and weakening of synapses occurring with distinct patterns of activity (neuronal “experience”). These plastic changes can be transient (lasting seconds to minutes) or can persist for days to months. Long-lasting forms of synaptic plasticity are supported by the de novo synthesis of macromolecules. This process can be broadly divided into transcription of DNA into new messenger RNAs and translation of mRNAs into new proteins. A very useful experimental platform for studying these processes is the rodent ex vivo hippocampal slice preparation. Hippocampal slices can be utilized for pharmacological, biochemical, and electrophysiological experiments aimed at studying mechanisms upstream and downstream of the macromolecular synthesis underlying persistent synaptic plasticity.

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References

  1. Krug M, Lossner B, Ott T (1984) Anisomycin blocks the late phase of long-term potentiation in the dentate gyrus of freely moving rats. Brain Res Bull 13(1):39–42

    Article  PubMed  CAS  Google Scholar 

  2. Stanton PK, Sarvey JM (1984) Blockade of long-term potentiation in rat hippocampal CA1 region by inhibitors of protein synthesis. J Neurosci 4(12):3080–3088

    PubMed  CAS  Google Scholar 

  3. Nguyen PV, Abel T, Kandel ER (1994) Requirement of a critical period of transcription for induction of a late phase of LTP. Science 265(5175):1104–1107

    Article  PubMed  CAS  Google Scholar 

  4. Frey U et al (1996) Influence of actinomycin D, a RNA synthesis inhibitor, on long-term potentiation in rat hippocampal neurons in vivo and in vitro. J Physiol 490(pt 3):703–711

    PubMed  CAS  Google Scholar 

  5. Frey U, Morris RG (1997) Synaptic tagging and long-term potentiation. Nature 385(6616):533–536

    Article  PubMed  CAS  Google Scholar 

  6. Scharfman HE et al (2001) Survival of dentate hilar mossy cells after pilocarpine-induced seizures and their synchronized burst discharges with area CA3 pyramidal cells. Neuroscience 104(3):741–759

    Article  PubMed  CAS  Google Scholar 

  7. Flicker C, Geyer MA (1982) The hippocampus as a possible site of action for increased locomotion during intracerebral infusions of norepinephrine. Behav Neural Biol 34(4):421–426

    Article  PubMed  CAS  Google Scholar 

  8. Stevens R (1973) Probability discrimination learning in hippocampectomized rats. Physiol Behav 10(6):1023–1027

    Article  PubMed  CAS  Google Scholar 

  9. O’Keefe J, Dostrovsky J (1971) The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Res 34(1):171–175

    Article  PubMed  Google Scholar 

  10. Nonneman AJ, Voigt J, Kolb BE (1974) Comparisons of behavioral effects of hippocampal and prefrontal cortex lesions in the rat. J Comp Physiol Psychol 87(2): 249–260

    Article  PubMed  CAS  Google Scholar 

  11. Penner R (1995) Single channel recording. In: Sakmann B, Neher E (eds) Part I. A practical guide to patch clamping, 2nd edn. Springer, New York, pp 3–30

    Google Scholar 

  12. Finkel A, Bookman R (2001) The electrophysiology setup. Curr Protoc Neurosci Chapter 6:Unit 6.1

    Google Scholar 

  13. Capron B et al (2006) The characteristics of LTP induced in hippocampal slices are dependent on slice-recovery conditions. Learn Mem 13(3):271–277

    Article  PubMed  CAS  Google Scholar 

  14. Dudek FE, Obenaus A, Tasker JG (1990) Osmolality-induced changes in extracellular volume alter epileptiform bursts independent of chemical synapses in the rat: importance of non-synaptic mechanisms in hippocampal epileptogenesis. Neurosci Lett 120(2):267–270

    Article  PubMed  CAS  Google Scholar 

  15. Haas HL, Gahwiler BH (1992) Vasoactive intestinal polypeptide modulates neuronal excitability in hippocampal slices of the rat. Neuroscience 47(2):273–277

    Article  PubMed  CAS  Google Scholar 

  16. Schuchmann S et al (2002) Synaptic and nonsynaptic ictogenesis occurs at different temperatures in submerged and interface rat brain slices. J Neurophysiol 87(6):2929–2935

    PubMed  CAS  Google Scholar 

  17. Kettenmann H, Grantyn R (eds) (1992) Practical electrophysiological methods: a guide for in vitro studies in vertebrate neurobiology. Wiley-Liss, New York, p 468

    Google Scholar 

  18. Bretschneider F, de Weille JR (2006) Introduction to electrophysiological methods and instrumentation, 1st edn. Elsevier, San Diego, p 266

    Google Scholar 

  19. Hemmings HC Jr et al (2005) The general anesthetic isoflurane depresses synaptic vesicle exocytosis. Mol Pharmacol 67(5):1591–1599

    Article  PubMed  CAS  Google Scholar 

  20. Poschel B, Stanton PK (2007) Comparison of cellular mechanisms of long-term depression of synaptic strength at perforant path-granule cell and Schaffer collateral-CA1 synapses. Prog Brain Res 163:473–500

    Article  PubMed  CAS  Google Scholar 

  21. Malenka RC, Bear MF (2004) LTP and LTD: an embarrassment of riches. Neuron 44(1): 5–21

    Article  PubMed  CAS  Google Scholar 

  22. Bear MF, Malenka RC (1994) Synaptic plasticity: LTP and LTD. Curr Opin Neurobiol 4(3):389–399

    Article  PubMed  CAS  Google Scholar 

  23. Bellone C, Luscher C, Mameli M (2008) Mechanisms of synaptic depression triggered by metabotropic glutamate receptors. Cell Mol Life Sci 65(18):2913–2923

    Article  PubMed  CAS  Google Scholar 

  24. Manahan-Vaughan D, Braunewell KH (1999) Novelty acquisition is associated with induction of hippocampal long-term depression. Proc Natl Acad Sci U S A 96(15):8739–8744

    Article  PubMed  CAS  Google Scholar 

  25. Manahan-Vaughan D, Braunewell KH (2005) The metabotropic glutamate receptor, mGluR5, is a key determinant of good and bad spatial learning performance and hippocampal synaptic plasticity. Cereb Cortex 15(11):1703–1713

    Article  PubMed  Google Scholar 

  26. Bear MF, Abraham WC (1996) Long-term depression in hippocampus. Annu Rev Neurosci 19:437–462

    Article  PubMed  CAS  Google Scholar 

  27. Huber KM, Kayser MS, Bear MF (2000) Role for rapid dendritic protein synthesis in hippocampal mGluR-dependent long-term depression. Science 288(5469):1254–1257

    Article  PubMed  CAS  Google Scholar 

  28. Huber KM, Roder JC, Bear MF (2001) Chemical induction of mGluR5- and protein synthesis-dependent long-term depression in hippocampal area CA1. J Neurophysiol 86(1):321–325

    PubMed  CAS  Google Scholar 

  29. Ostroff LE et al (2002) Polyribosomes redistribute from dendritic shafts into spines with enlarged synapses during LTP in developing rat hippocampal slices. Neuron 35(3): 535–545

    Article  PubMed  CAS  Google Scholar 

  30. Dudek SM, Bear MF (1992) Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade. Proc Natl Acad Sci U S A 89(10):4363–4367

    Article  PubMed  CAS  Google Scholar 

  31. Manahan-Vaughan D, Kulla A, Frey JU (2000) Requirement of translation but not transcription for the maintenance of long-term depression in the CA1 region of freely moving rats. J Neurosci 20(22):8572–8576

    PubMed  CAS  Google Scholar 

  32. Huang YY, Li XC, Kandel ER (1994) cAMP contributes to mossy fiber LTP by initiating both a covalently mediated early phase and macromolecular synthesis-dependent late phase. Cell 79(1):69–79

    Article  PubMed  CAS  Google Scholar 

  33. Banko JL et al (2005) The translation repressor 4E-BP2 is critical for eIF4F complex formation, synaptic plasticity, and memory in the hippocampus. J Neurosci 25(42):9581–9590

    Article  PubMed  CAS  Google Scholar 

  34. Hoeffer CA et al (2008) Removal of FKBP12 enhances mTOR-raptor interactions, LTP, memory, and perseverative/repetitive behavior. Neuron 60(5):832–845

    Article  PubMed  CAS  Google Scholar 

  35. Namgung U, Valcourt E, Routtenberg A (1995) Long-term potentiation in vivo in the intact mouse hippocampus. Brain Res 689(1):85–92

    Article  PubMed  CAS  Google Scholar 

  36. Chen HX, Otmakhov N, Lisman J (1999) Requirements for LTP induction by pairing in hippocampal CA1 pyramidal cells. J Neurophysiol 82(2):526–532

    PubMed  CAS  Google Scholar 

  37. Abraham WC (1996) Induction of heterosynaptic and homosynaptic LTD in hippocampal sub-regions in vivo. J Physiol Paris 90(5–6): 305–306

    Article  PubMed  CAS  Google Scholar 

  38. Straube T, Frey JU (2003) Involvement of beta-adrenergic receptors in protein synthesis-dependent late long-term potentiation (LTP) in the dentate gyrus of freely moving rats: the critical role of the LTP induction strength. Neuroscience 119(2):473–479

    Article  PubMed  CAS  Google Scholar 

  39. Gelinas JN, Nguyen PV (2005) Beta-adrenergic receptor activation facilitates induction of a protein synthesis-dependent late phase of long-term potentiation. J Neurosci 25(13):3294–3303

    Article  PubMed  CAS  Google Scholar 

  40. Straube T et al (2003) Requirement of beta-adrenergic receptor activation and protein synthesis for LTP-reinforcement by novelty in rat dentate gyrus. J Physiol 552(pt 3): 953–960

    Article  PubMed  CAS  Google Scholar 

  41. Tenorio G et al (2010) ‘Silent’ priming of translation-dependent LTP by beta-adrenergic receptors involves phosphorylation and recruitment of AMPA receptors. Learn Mem 17(12):627–638

    Article  PubMed  CAS  Google Scholar 

  42. Gingras AC et al (1999) Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism. Genes Dev 13(11):1422–1437

    Article  PubMed  CAS  Google Scholar 

  43. Banko JL, Klann E (2008) Cap-dependent translation initiation and memory. Prog Brain Res 169:59–80

    Article  PubMed  CAS  Google Scholar 

  44. Klann E, Dever TE (2004) Biochemical mechanisms for translational regulation in synaptic plasticity. Nat Rev Neurosci 5(12): 931–942

    Article  PubMed  CAS  Google Scholar 

  45. Pause A et al (1994) Dominant negative mutants of mammalian translation initiation factor eIF-4A define a critical role for eIF-4F in cap-dependent and cap-independent initiation of translation. EMBO J 13(5): 1205–1215

    PubMed  CAS  Google Scholar 

  46. Poulin F et al (1998) 4E-BP3, a new member of the eukaryotic initiation factor 4E-binding protein family. J Biol Chem 273(22): 14002–14007

    Article  PubMed  CAS  Google Scholar 

  47. Pause A et al (1994) Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5′-cap function. Nature 371(6500):762–767

    Article  PubMed  CAS  Google Scholar 

  48. Haghighat A et al (1995) Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E. EMBO J 14(22):5701–5709

    PubMed  CAS  Google Scholar 

  49. Bagni C, Greenough WT (2005) From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome. Nat Rev Neurosci 6(5):376–387

    Article  PubMed  CAS  Google Scholar 

  50. Weiler IJ et al (1997) Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation. Proc Natl Acad Sci U S A 94(10):5395–5400

    Article  PubMed  CAS  Google Scholar 

  51. Antar LN et al (2004) Metabotropic glutamate receptor activation regulates fragile x mental retardation protein and FMR1 mRNA localization differentially in dendrites and at synapses. J Neurosci 24(11):2648–2655

    Article  PubMed  CAS  Google Scholar 

  52. Ferrari F et al (2007) The fragile X mental retardation protein-RNP granules show an mGluR-dependent localization in the post-synaptic spines. Mol Cell Neurosci 34(3): 343–354

    Article  PubMed  CAS  Google Scholar 

  53. Bear MF, Huber KM, Warren ST (2004) The mGluR theory of fragile X mental retardation. Trends Neurosci 27(7):370–377

    Article  PubMed  CAS  Google Scholar 

  54. Napoli I et al (2008) The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP. Cell 134(6):1042–1054

    Article  PubMed  CAS  Google Scholar 

  55. Qin M et al (2005) Postadolescent changes in regional cerebral protein synthesis: an in vivo study in the FMR1 null mouse. J Neurosci 25(20):5087–5095

    Article  PubMed  CAS  Google Scholar 

  56. Huber KM et al (2002) Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc Natl Acad Sci U S A 99(11):7746–7750

    Article  PubMed  CAS  Google Scholar 

  57. Hou L et al (2006) Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression. Neuron 51(4):441–454

    Article  PubMed  CAS  Google Scholar 

  58. Tenson T, Mankin A (2006) Antibiotics and the ribosome. Mol Microbiol 59(6): 1664–1677

    Article  PubMed  CAS  Google Scholar 

  59. Kelly A, Mullany PM, Lynch MA (2000) Protein synthesis in entorhinal cortex and long-term potentiation in dentate gyrus. Hippocampus 10(4):431–437

    Article  PubMed  CAS  Google Scholar 

  60. Proud CG (2007) Signalling to translation: how signal transduction pathways control the protein synthetic machinery. Biochem J 403(2):217–234

    Article  PubMed  CAS  Google Scholar 

  61. Wang X, Proud CG (2007) Methods for studying signal-dependent regulation of translation factor activity. Methods Enzymol 431:113–142

    Article  PubMed  CAS  Google Scholar 

  62. Bottley A et al (2010) eIF4A inhibition allows translational regulation of mRNAs encoding proteins involved in Alzheimer’s disease. PLoS One 5(9):e13030

    Article  PubMed  Google Scholar 

  63. Marnef A, Standart N (2010) Pat1 proteins: a life in translation, translation repression and mRNA decay. Biochem Soc Trans 38(6):1602–1607

    Article  PubMed  CAS  Google Scholar 

  64. Thomas JR, Hergenrother PJ (2008) Targeting RNA with small molecules. Chem Rev 108(4):1171–1224

    Article  PubMed  CAS  Google Scholar 

  65. Martin DP et al (1988) Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation. J Cell Biol 106(3):829–844

    Article  PubMed  CAS  Google Scholar 

  66. Rosenblum K, Meiri N, Dudai Y (1993) Taste memory: the role of protein synthesis in gustatory cortex. Behav Neural Biol 59(1): 49–56

    Article  PubMed  CAS  Google Scholar 

  67. Meiri N, Rosenblum K (1998) Lateral ventricle injection of the protein synthesis inhibitor anisomycin impairs long-term memory in a spatial memory task. Brain Res 789(1): 48–55

    Article  PubMed  CAS  Google Scholar 

  68. Nader K, Schafe GE, Le Doux JE (2000) Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406(6797):722–726

    Article  PubMed  CAS  Google Scholar 

  69. Alberini CM (2008) The role of protein synthesis during the labile phases of memory: revisiting the skepticism. Neurobiol Learn Mem 89(3):234–246

    Article  PubMed  CAS  Google Scholar 

  70. Dever TE (2002) Gene-specific regulation by general translation factors. Cell 108(4):545–556

    Article  PubMed  CAS  Google Scholar 

  71. Kim DH et al (2002) mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110(2):163–175

    Article  PubMed  CAS  Google Scholar 

  72. Moerke NJ et al (2007) Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell 128(2):257–267

    Article  PubMed  CAS  Google Scholar 

  73. Kozak M (1991) Structural features in eukaryotic mRNAs that modulate the initiation of translation. J Biol Chem 266(30): 19867–19870

    PubMed  CAS  Google Scholar 

  74. Kozak M (1989) Circumstances and mechanisms of inhibition of translation by secondary structure in eucaryotic mRNAs. Mol Cell Biol 9(11):5134–5142

    PubMed  CAS  Google Scholar 

  75. Pelletier J, Sonenberg N (1987) The involvement of mRNA secondary structure in protein synthesis. Biochem Cell Biol 65(6):576–581

    Article  PubMed  CAS  Google Scholar 

  76. Costa-Mattioli M et al (2009) Translational control of long-lasting synaptic plasticity and memory. Neuron 61(1):10–26

    Article  PubMed  CAS  Google Scholar 

  77. Selcher JC et al (2003) A role for ERK MAP kinase in physiologic temporal integration in hippocampal area CA1. Learn Mem 10(1):26–39

    Article  PubMed  Google Scholar 

  78. Adams JP et al (2000) MAPK regulation of gene expression in the central nervous system. Acta Neurobiol Exp (Wars) 60(3):377–394

    CAS  Google Scholar 

  79. Subramaniam S, Unsicker K (2010) ERK and cell death: ERK1/2 in neuronal death. FEBS J 277(1):22–29

    Article  PubMed  CAS  Google Scholar 

  80. Sweatt JD (2004) Mitogen-activated protein kinases in synaptic plasticity and memory. Curr Opin Neurobiol 14(3):311–317

    Article  PubMed  CAS  Google Scholar 

  81. Kelleher RJ III et al (2004) Translational control by MAPK signaling in long-term synaptic plasticity and memory. Cell 116(3):467–479

    Article  PubMed  CAS  Google Scholar 

  82. Banko JL, Hou L, Klann E (2004) NMDA receptor activation results in PKA- and ERK-dependent Mnk1 activation and increased eIF4E phosphorylation in hippocampal area CA1. J Neurochem 91(2):462–470

    Article  PubMed  CAS  Google Scholar 

  83. Burnette WN (2009) Western blotting: remembrance of past things. Methods Mol Biol 536:5–8

    Article  PubMed  CAS  Google Scholar 

  84. Lalonde S et al (2008) Molecular and cellular approaches for the detection of protein-protein interactions: latest techniques and current limitations. Plant J 53(4):610–635

    Article  PubMed  CAS  Google Scholar 

  85. Berggard T, Linse S, James P (2007) Methods for the detection and analysis of protein-protein interactions. Proteomics 7(16):2833–2842

    Article  PubMed  Google Scholar 

  86. Phizicky EM, Fields S (1995) Protein-protein interactions: methods for detection and analysis. Microbiol Rev 59(1):94–123

    PubMed  CAS  Google Scholar 

  87. Hoeffer CA, Klann E (2010) mTOR signaling: at the crossroads of plasticity, memory and disease. Trends Neurosci 33(2):67–75

    Article  PubMed  CAS  Google Scholar 

  88. Sarbassov DD et al (2004) Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 14(14):1296–1302

    Article  PubMed  CAS  Google Scholar 

  89. Banko JL et al (2006) Regulation of eukaryotic initiation factor 4E by converging signaling pathways during metabotropic glutamate receptor-dependent long-term depression. J Neurosci 26(8):2167–2173

    Article  PubMed  CAS  Google Scholar 

  90. Sharma A et al (2010) Dysregulation of mTOR signaling in fragile X syndrome. J Neurosci 30(2):694–702

    Article  PubMed  CAS  Google Scholar 

  91. Schmidt EK et al (2009) SUnSET, a nonradioactive method to monitor protein synthesis. Nat Methods 6(4):275–277

    Article  PubMed  CAS  Google Scholar 

  92. Hoeffer CA et al (2011) Inhibition of the interactions between eukaryotic initiation factors 4E and 4G impairs long-term associative memory consolidation but not reconsolidation. Proc Natl Acad Sci U S A 108(8):3383–3388

    Article  PubMed  CAS  Google Scholar 

  93. Nguyen PV, Duffy SN, Young JZ (2000) Differential maintenance and frequency-dependent tuning of LTP at hippocampal synapses of specific strains of inbred mice. J Neurophysiol 84(5):2484–2493

    PubMed  CAS  Google Scholar 

  94. Schimanski LA et al (2007) Impaired hippocampal LTP in inbred mouse strains can be rescued by beta-adrenergic receptor activation. Eur J Neurosci 25(5):1589–1598

    Article  PubMed  Google Scholar 

  95. Prakash S et al (2009) Genetic differences in hippocampal synaptic plasticity. Neuroscience 161(2):342–346

    Article  PubMed  CAS  Google Scholar 

  96. Miguens M et al (2011) Depotentiation of hippocampal long-term potentiation depends on genetic background and is modulated by cocaine self-administration. Neuroscience 187:36–42

    Article  PubMed  CAS  Google Scholar 

  97. Sajikumar S, Navakkode S, Frey JU (2005) Protein synthesis-dependent long-term functional plasticity: methods and techniques. Curr Opin Neurobiol 15(5):607–613

    Article  PubMed  CAS  Google Scholar 

  98. Frey U, Morris RG (1998) Weak before strong: dissociating synaptic tagging and plasticity-factor accounts of late-LTP. Neuropharmacology 37(4–5):54f5–54f52

    Google Scholar 

  99. Deadwyler SA, Dunwiddie T, Lynch G (1987) A critical level of protein synthesis is required for long-term potentiation. Synapse 1(1):90–95

    Article  PubMed  CAS  Google Scholar 

  100. Osten P et al (1996) Protein synthesis-dependent formation of protein kinase Mzeta in long-term potentiation. J Neurosci 16(8): 2444–2451

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Physiology and Neuroscience, Smilow Neuroscience Program, School of Medicine, New York University, New York, NY, USA

    Charles A. Hoeffer

  2. Center for Neural Science, New York University, New York, NY, USA

    Emanuela Santini & Eric Klann

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  1. Charles A. Hoeffer
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  2. Emanuela Santini
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  3. Eric Klann
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Editors and Affiliations

  1. School of Medicine, Department of Physiology, University of Alberta, Medical Sciences Building 7-14, Edmonton, T6G 2H7, Alberta, Canada

    Peter Nguyen

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Hoeffer, C.A., Santini, E., Klann, E. (2013). Translational Regulation of Synaptic Plasticity. In: Nguyen, P. (eds) Multidisciplinary Tools for Investigating Synaptic Plasticity. Neuromethods, vol 81. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-517-0_4

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  • DOI: https://doi.org/10.1007/978-1-62703-517-0_4

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