DNA Methylation in Memory Formation

Chapter
First Online:
Part of the Research and Perspectives in Neurosciences book series (NEUROSCIENCE)

Abstract

The mechanism by which behavioral memories are able to endure in a structure as dynamic as the brain is a long-standing mystery of cognition. For example, a memory must survive, by some mechanism, the ongoing replacement of the proteins that were initially responsible for its formation. In this review I describe the beginning of work designed to test the hypothesis that the brain utilizes DNA methylation as a mechanism to contribute to the stable maintenance of memories. Decades ago, both Francis Crick and Robin Holliday speculated that DNA methylation might be a self-perpetuating mechanism involved in memory storage. Ongoing studies in a number of laboratories are testing the idea that learning-induced epigenetic modifications in the cortex can serve as stable alterations in brain cells, contributing to the support of memory stability. Thinking in analogy to developmental biology, oncogenesis, and cellular differentiation, investigators in this area have begun to pursue the possibility that chromatin- and DNA-modifying molecular mechanisms might play a role in memory in the adult CNS.

Keywords

Anterior Cingulate Cortex Memory Formation Fear Memory Contextual Fear Conditioning Remote Memory 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. Alarcon JM, Malleret G, Touzani K, Vronskaya S, Ishii S, Kandel ER, Barco A (2004) Chromatin acetylation, memory, and LTP are impaired in CBP+/− mice. Neuron 42:947–959PubMedCrossRefGoogle Scholar
  2. Barrett RM, Wood MA (2008) Beyond transcription factors: the role of chromatin modifying enzymes in regulating transcription required for memory. Learn Mem 15:460–467PubMedCrossRefGoogle Scholar
  3. Beffert U, Weeber EJ, Durudas A, Qiu S, Masiulis I, Sweatt JD, Li WP, Adelmann G, Frotscher M, Hammer RE, Herz J. (2005) Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2. Neuron 47(4):567–79CrossRefGoogle Scholar
  4. Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, Zoghbi HY (2008) MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320:1224–1229PubMedCrossRefGoogle Scholar
  5. Collins AL, Levenson JM, Vilaythong AP, Richman R, Armstrong DL, Noebels JL, Sweatt JD, Zoghbi HY (2004) Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Hum Mol Genet 13:2679–2689PubMedCrossRefGoogle Scholar
  6. Crick F (1984) Memory and molecular turnover. Nature 312:101PubMedCrossRefGoogle Scholar
  7. Day JJ, Sweatt JD (2010) DNA methylation and memory formation. Nat Neurosci 13:1319–1323PubMedCrossRefGoogle Scholar
  8. Feng J, Zhou Y, Campbell SL, Le T, Li E, Sweatt JD, Silva AJ, Fan G (2010) Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons. Nat Neurosci 13:423–430PubMedCrossRefGoogle Scholar
  9. Frankland PW, Bontempi B, Talton LE, Kaczmarek L, Silva AJ (2004) The involvement of the anterior cingulate cortex in remote contextual fear memory. Science 304:881–883PubMedCrossRefGoogle Scholar
  10. Graff J, Mansuy IM (2008) Epigenetic codes in cognition and behaviour. Behav Brain Res 192:70–87PubMedCrossRefGoogle Scholar
  11. Holliday R (1999) Is there an epigenetic component in long-term memory? J Theor Biol 200:339–341PubMedCrossRefGoogle Scholar
  12. Jiang Y, Langley B, Lubin FD, Renthal W, Wood MA, Yasui DH, Kumar A, Nestler EJ, Akbarian S, Beckel-Mitchener A (2008) Epigenetics in the nervous system. J Neurosci 28:11753–11759PubMedCrossRefGoogle Scholar
  13. Kangaspeska S, Kangaspeska S, Stride B, Métivier R, Polycarpou-Schwarz M, Ibberson D, Carmouche RP, Benes V, Gannon F, Reid G (2008) Transient cyclical methylation of promoter DNA. Nature 452:112–115PubMedCrossRefGoogle Scholar
  14. Kessels HW, Malinow R (2009) Synaptic AMPA receptor plasticity and behavior. Neuron 61:340–350PubMedCrossRefGoogle Scholar
  15. Korzus E, Rosenfeld MG, Mayford M (2004) CBP histone acetyltransferase activity is a critical component of memory consolidation. Neuron 42:961–972PubMedCrossRefGoogle Scholar
  16. Kriaucionis S, Heintz N (2009) The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324:929–930PubMedCrossRefGoogle Scholar
  17. Levenson JM, Choi S, Lee SY, Cao YA, Ahn HJ, Worley KC, Pizzi M, Liou HC, Sweatt JD (2004) Regulation of histone acetylation during memory formation in the hippocampus. J Biol Chem 279:40545–40559PubMedCrossRefGoogle Scholar
  18. Levenson JM, Roth TL, Lubin FD, Miller CA, Huang IC, Desai P, Malone LM, Sweatt JD (2006) Evidence that DNA (cytosine-5) methyltransferase regulates synaptic plasticity in the hippocampus. J Biol Chem 281:15763–15773PubMedCrossRefGoogle Scholar
  19. Liu L, Van Groen T, Kadish I, Tollefsbol TO (2009) DNA methylation impacts on learning and memory in aging. Neurobiol Aging 30:549–560PubMedCrossRefGoogle Scholar
  20. Lubin FD, Sweatt JD (2007) The IkappaB kinase regulates chromatin structure during reconsolidation of conditioned fear memories. Neuron 55:942–957PubMedCrossRefGoogle Scholar
  21. Lubin FD, Roth TL, Sweatt JD (2008) Epigenetic regulation of bdnf gene transcription in the consolidation of fear memory. J Neurosci 28:10576–10586PubMedCrossRefGoogle Scholar
  22. Ma DK, Guo JU, Ming GL, Song H (2009a) DNA excision repair proteins and Gadd45 as molecular players for active DNA demethylation. Cell Cycle 8:1526–1531PubMedCrossRefGoogle Scholar
  23. Ma DK, Jang MH, Guo JU, Kitabatake Y, Chang ML, Pow-Anpongkul N, Flavell RA, Lu B, Ming GL, Song H (2009b) Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science 323:1074–1077PubMedCrossRefGoogle Scholar
  24. Malleret G, Haditsch U, Genoux D, Jones MW, Bliss TV, Vanhoose AM, Weitlauf C, Kandel ER, Winder DG, Mansuy IM (2001) Inducible and reversible enhancement of learning, memory and long-term potentiation by inhibition of calcineurin. Cell 104:675–686PubMedGoogle Scholar
  25. McCormack MG, Stornetta RL, Zhu JJ (2006) Synaptic AMPA receptor exchange maintains bidirectional plasticity. Neuron 60:75–88CrossRefGoogle Scholar
  26. Meaney MJ, Szyf M (2005a) Maternal care as a model for experience-dependent chromatin plasticity? Trends Neurosci 28:456–463PubMedCrossRefGoogle Scholar
  27. Meaney MJ, Szyf M (2005b) Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome. Dialogues Clin Neurosci 7:103–123PubMedGoogle Scholar
  28. Métivier R, Gallais R, Tiffoche C, Le Péron C, Jurkowska RZ, Carmouche RP, Ibberson D, Barath P, Demay F, Reid G, Benes V, Jeltsch A, Gannon F, Salbert G (2008) Cyclical DNA methylation of a transcriptionally active promoter. Nature 452:45–50PubMedCrossRefGoogle Scholar
  29. Miller CA, Sweatt JD (2007) Covalent modification of DNA regulates memory formation. Neuron 53:857–869PubMedCrossRefGoogle Scholar
  30. Miller CA, Campbell SL, Sweatt JD (2008) DNA methylation and histone acetylation work in concert to regulate memory formation and synaptic plasticity. Neurobiol Learn Mem 89:599–603PubMedCrossRefGoogle Scholar
  31. Miller CA, Gavin CF, White JA, Parrish RR, Honasoge A, Yancey CR, Rivera IM, Rubio MD, Rumbaugh G, Sweatt JD (2010) Cortical DNA methylation maintains remote memory. Nat Neurosci 13:664–666PubMedCrossRefGoogle Scholar
  32. Moretti P, Levenson JM, Battaglia F, Atkinson R, Teague R, Antalffy B, Armstrong D, Arancio O, Sweatt JD, Zoghbi HY (2006) Synaptic plasticity and learning and memory are impaired in a mouse model of Rett syndrome. J Neurosci 26:319–327PubMedCrossRefGoogle Scholar
  33. Nelson ED, Kavalali ET, Monteggia LM (2008) Activity-dependent suppression of miniature neurotransmission through the regulation of DNA methylation. J Neurosci 28:395–406PubMedCrossRefGoogle Scholar
  34. Ooi SK, Bestor TH (2008) The colorful history of active DNA demethylation. Cell 133:1145–1148PubMedCrossRefGoogle Scholar
  35. Restivo L, Vetere G, Bontempi B, Ammassari-Teule M (2009) The formation of recent and remote memory is associated with time-dependent formation of spines in the hippocampus and anterior cingulate cortex. J Neurosci 29:8206–8214PubMedCrossRefGoogle Scholar
  36. Roberson ED, Sweatt JD (1999) A biochemical blueprint for long-term memory. Learn Mem 6:381–388PubMedGoogle Scholar
  37. Sanders MJ, Fanselow MS (2003) Pre-training prevents context fear conditioning deficits produced by hippocampal NDMA receptor blockade. Neurobiol Learn Mem 80:123–129PubMedCrossRefGoogle Scholar
  38. Sweatt JD (2009) Experience-dependent epigenetic modifications in the central nervous system. Biol Psychiatry 65:191–197PubMedCrossRefGoogle Scholar
  39. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930–935PubMedCrossRefGoogle Scholar
  40. Wang SH, Teixeira CM, Wheeler AL, Frankland PW (2009) The precision of remote context memories does not require the hippocampus. Nat Neurosci 12:253–255PubMedCrossRefGoogle Scholar
  41. Weaver IC, Champagne FA, Brown SE, Dymov S, Sharma S, Meaney MJ, Szyf M (2005) Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: altering epigenetic marking later in life. J Neurosci 25:11045–11054PubMedCrossRefGoogle Scholar
  42. Weeber EJ, Beffert U, Jones C, Christian JM, Forster E, Sweatt JD, Herz J (2002) Reelin and ApoE receptors cooperate to enhance synaptic plasticity and learning. J Biol Chem 277:39944–39952PubMedCrossRefGoogle Scholar
  43. Wood MA, Attner MA, Oliveira AM, Brindle PK, Abel T (2006) A transcription factor-binding domain of the coactivator CBP is essential for long-term memory and the expression of specific target genes. Learn Mem 13:609–617PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Department of Neurobiology and Evelyn F. McKnight Brain InstituteUniversity of Alabama at BirminghamBirminghamUSA

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