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The Molecular Biology of Memory Storage: A Dialog Between Genes and Synapses

  • Nobel Lecture
  • Published:
Bioscience Reports

Abstract

The biology of learning, and short-term and long-term memory, as revealed by Aplysia and other organisms, is reviewed.

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References

  1. E. R. Kandel W. A. Spencer (1961) ArticleTitleElectrophysiological properties of an archicortical neuron In Problems in Electrobiology Ann. N.Y. Acad. Sci 94 570–603 Occurrence Handle13751137

    PubMed  Google Scholar 

  2. W. H. Thorpe (1963) Learning and Instinct in Animals. Revised Edition Cambridge Harvard University Press, Mass

    Google Scholar 

  3. W. T. Frazier E. R. Kandel I. Kupfermann R. Waziri R. E. Coggeshall (1967) ArticleTitleMorphological and functional properties of identified neurons in the abdominal ganglion of Aplysiacalifornica J. Neurophysiol 30 1288–1351

    Google Scholar 

  4. I. Kupfermann E.R. Kandel (1969) ArticleTitleNeuronal controls of a behavioral response mediated by the abdominal ganglion of Aplysia Science 164 847–850 Occurrence Handle5767790

    PubMed  Google Scholar 

  5. H. Pinsker I. Kupfermann V. Castellucci E. R. Kandel (1970) ArticleTitleHabituation and dishabituation of the gill-withdrawal reflex in Aplysia Science 167 1740–1742 Occurrence Handle5416541

    PubMed  Google Scholar 

  6. I. Kupfermann V. Castellucci H. Pinsker E. R. Kandel (1970) ArticleTitleNeuronal correlates of habituation and dishabituation of the gill-withdrawal reflex in Aplysia Science 167 1743–1745 Occurrence Handle5416542

    PubMed  Google Scholar 

  7. V. Castellucci H. Pinsker I. Kupfermann E. R. Kandel (1970) ArticleTitleNeuronal mechanisms of habituation and dishabituation of the gill-withdrawal reflex in Aplysia Science 167 1745–1748 Occurrence Handle5416543

    PubMed  Google Scholar 

  8. H. M. Pinsker W. A. Hening T. J. Carew E. R. Kandel (1973) ArticleTitleLong-term sensitization of a defensive withdrawal reflex in Aplysia Science 182 1039–1042 Occurrence Handle4748675

    PubMed  Google Scholar 

  9. T. J. Carew H. M. Pinsker E. R. Kandel (1972) ArticleTitleLong-term habituation of a defensive withdrawal reflex in Aplysia Science 175 451–454

    Google Scholar 

  10. W. N. Frost V. F. Castellucci R. D. Hawkins E. R. Kandel (1985) ArticleTitleMonosynaptic connections made by the sensory neurons of the gill- and siphon-withdrawal reflex in Aplysia participate in the storage of long-term memory for sensitization Proc. Natl. Acad. Sci. USA 82 8266–8269

    Google Scholar 

  11. J. Byrne V. Castellucci E. R. Kandel (1974) ArticleTitleReceptive fields and response properties of mechanoreceptor neurons innervating skin and mantle shelf of Aplysia J. Neurophysiol 37 1041–1064 Occurrence Handle4370315

    PubMed  Google Scholar 

  12. V. F. Castellucci H. Blumenfeld P. Goelet E. R. Kandel (1989) ArticleTitleInhibitor of protein synthesis blocks long-term behavioral sensitization in the isolated gill-withdrawal reflex of Aplysia J. Neurobiol 20 1–9 Occurrence Handle10.1002/neu.480200102 Occurrence Handle2921606

    Article  PubMed  Google Scholar 

  13. E. R. Kandel (1976) Cellular Basis of Behavior: An Introduction to Behavioral Biology Freeman San Francisco

    Google Scholar 

  14. E. R. Kandel (1978) A Cell-Biological Approach to Learning. Grass Lecture Monograph I Society Bethesda Md

    Google Scholar 

  15. E. R. Kandel (1979) The Behavioral Biology of Aplysia: A Contribution to the Comparative Study of Opisthobranch Molluscs Freeman San Francisco

    Google Scholar 

  16. S. R. Cajal (1894) ArticleTitleLa fine structure des centres nerveux, The Croonian Lecture Proc. R. Soc. Lond 55 444–468

    Google Scholar 

  17. E. R. Kandel W. A. Spencer (1968) ArticleTitleCellular neurophysiological approaches in the study of learning Physiol. Rev 48 65–134 Occurrence Handle4295027

    PubMed  Google Scholar 

  18. R. D. Hawkins V. F. Castellucci E. R. Kandel (1981) ArticleTitleInterneurons involved in mediation and modulation of the gill-withdrawal reflex in Aplysia. I. Identification and characterization J. Neurophysiol 45 304–314 Occurrence Handle7463107

    PubMed  Google Scholar 

  19. R. D. Hawkins V. F. Castellucci E. R. Kandel (1981) ArticleTitleInterneurons involved in mediation and modulation of the gill-withdrawal reflex in Aplysia. II. Identified neurons produce hetero-synaptic facilitation contributing to behavioral sensitization J. Neurophysiol 45 315–326 Occurrence Handle6257863

    PubMed  Google Scholar 

  20. T. J. Carew R. D. Hawkins E. R. Kandel (1983) ArticleTitleDifferential classical conditioning of a defensive withdrawal reflex in Aplysia californica Science 219 397–400 Occurrence Handle6681571

    PubMed  Google Scholar 

  21. R. D. Hawkins T. W. Abrams T. J. Carew E. R. Kandel (1983) ArticleTitleA cellular mechanism of classical conditioning in Aplysia: activity-dependent amplification of presynaptic facilitation Science 219 400–405 Occurrence Handle6294833

    PubMed  Google Scholar 

  22. J. H. Byrne V. F. Castellucci E. R. Kandel (1978) ArticleTitleContribution of individual mechanoreceptor sensory to defensive gill-withdrawal reflex in Aplysia J. Neurophysiol 41 418–431 Occurrence Handle650275

    PubMed  Google Scholar 

  23. T. J. Carew V. F. Castellucci E. R. Kandel (1979) ArticleTitleSensitization in Aplysia: restoration of transmission in synapses inactivated by long-term habituation Science 205 417–419 Occurrence Handle451611

    PubMed  Google Scholar 

  24. M. Klein E. R. Kandel (1980) ArticleTitleMechanism of calcium current modulation underlying presynaptic facilitation and behavioral sensitization in Aplysia Proc. Natl. Acad. Sci. USA 77 6912–6916 Occurrence Handle6256770

    PubMed  Google Scholar 

  25. M. Klein B. Hochner E. R. Kandel (1986) ArticleTitleFacilitatory transmitters and cAMP can modulate accommodation as well as transmitter release in Aplysia sensory neurons. evidence for parallel processing in a single cell Proc. Natl. Acad. Sci. USA 83 7994–7998

    Google Scholar 

  26. J. H. Schwartz V. F. Castellucci E. R. Kandel (1971) ArticleTitleFunctioning of identified neurons and synapses in abdominal ganglion of Aplysia in absence of protein synthesis J. Neurophysiol 34 939–953 Occurrence Handle4329963

    PubMed  Google Scholar 

  27. H. Cedar E. R. Kandel J. H. Schwartz (1972) ArticleTitleCyclic adenosine monophosphate in the nervous system of Aplysia californica. I. Increased synthesis in response to synaptic stimulation J. Gen. Physiol 60 558–569 Occurrence Handle10.1085/jgp.60.5.558 Occurrence Handle4345439

    Article  PubMed  Google Scholar 

  28. A. R. Kriegstein V. Castellucci E. R. Kandel (1974) ArticleTitleMetamorphosis of Aplysiacalifornica in laboratory culture Proc. Natl. Acad. Sci. USA 71 3654–3658 Occurrence Handle4530325

    PubMed  Google Scholar 

  29. H. Cedar J. H. Schwartz (1972) ArticleTitleCyclic adenosine monophosphate in the nervous system of Aplysia california. II. Effect of serotonin and dopamine J. Gen. Physiol 60 570–587 Occurrence Handle10.1085/jgp.60.5.570 Occurrence Handle4345440

    Article  PubMed  Google Scholar 

  30. V. Castellucci E. R. Kandel (1974) ArticleTitleA quantal analysis of the synaptic depression underlying habituation of the gill-withdrawal reflex in Aplysia Proc. Natl. Acad. Sci. USA 71 5004–5008 Occurrence Handle4373738

    PubMed  Google Scholar 

  31. V. Castellucci E. R. Kandel (1976) ArticleTitlePresynaptic facilitation as a mechanism for behavioral sensitization in Aplysia Science 194 1176–1178 Occurrence Handle11560

    PubMed  Google Scholar 

  32. M. Brunelli V. Castellucci E. R. Kandel (1976) ArticleTitleSynaptic facilitation and behavioral sensitisation in Aplysia: Possible role of serotonin and cyclic AMP Science 194 1178–1181 Occurrence Handle186870

    PubMed  Google Scholar 

  33. E. R. Kandel M. Brunelli J. Byrne V. Castellucci (1976) ArticleTitleA common presynaptic locus for the synaptic changes underlying short-term habituation and sensitization of the gill-withdrawal reflex in Aplysia Cold Spring Harbor Symp. Quant. Biol 40 465–482 Occurrence Handle181201

    PubMed  Google Scholar 

  34. D. L. Glanzman S. L. Mackey R. D. Hawkins A. M. Dyke P. E. Lloyd E. R. Kandel (1989) ArticleTitleDepletion of serotonin in the nervous system of Aplysia reduces the behavioral enhancement of gill withdrawal as well as the heterosynaptic facilitation produces by tail shock J. Neurosci 9 4200–4213 Occurrence Handle2592997

    PubMed  Google Scholar 

  35. S. L. Mackay E. R. Kandel R. D. Hawkins (1989) ArticleTitleIdentified serotonergic neurons LCB1 and RCB1 in the cerebral ganglia of Aplysia produce presynaptic facilitation of siphon sensory neurons J. Neurosci 9 4227–4235 Occurrence Handle2592999

    PubMed  Google Scholar 

  36. J. H. Byrne V. F. Castellucci T. J. Carew E. R. Kandel (1978) ArticleTitleStimulus-response relations and stability of mechanoreceptor and motor neurons mediating defensive gill-withdrawal reflex in Aplysia J. Neurophysiol 41 402–417 Occurrence Handle650274

    PubMed  Google Scholar 

  37. V. F. Castellucci E. R. Kandel J. H. Schwartz F. D. Wilson A. C. Nairn P. Greengard (1980) ArticleTitleIntracellular injection of the catalytic subunit of cyclic AMP-dependent protein kinase simulates facilitation of transmitter release underlying behavioral sensitization in Aplysia Proc. Natl. Acad. Sci. USA 77 7492–7496 Occurrence Handle6111794

    PubMed  Google Scholar 

  38. V. F. Castellucci A. Nairn P. Greengard J. H. Schwartz E. R. Kandel (1982) ArticleTitleInhibitor of adenosine 3′:5′-monophosphate-dependent protein kinase blocks presynaptic facilitation in Aplysia J. Neurosci 2 1673–1681 Occurrence Handle6292379

    PubMed  Google Scholar 

  39. S. Siegelbaum J. S. Camardo E. R. Kandel (1982) ArticleTitleSerotonin and cAMP close single K+ channels in Aplysia sensory neurons Nature 299 413–417 Occurrence Handle10.1038/299413a0 Occurrence Handle6289122

    Article  PubMed  Google Scholar 

  40. M. J. Shuster J. S. Camardo S. A. Siegelbaum E. R. Kandel (1985) ArticleTitleCyclic AMP-dependent protein kinase closes the serotonin-sensitive K+ channels of Aplysia sensory neurons in cell-free membrane patches Nature 313 392–395 Occurrence Handle10.1038/313392a0 Occurrence Handle2578623

    Article  PubMed  Google Scholar 

  41. J. H. Byrne E. R. Kandel (1995) ArticleTitlePresynaptic facilitation revisited: state and time dependence J. Neurosci 16 425–435

    Google Scholar 

  42. S. G. Rayport S. Schacher (1986) ArticleTitleSynaptic plasticity in vitro: cell culture of identified Aplysia neurons mediating short-term habituation and sensitization J. Neurosci 6 759–763 Occurrence Handle3958793

    PubMed  Google Scholar 

  43. P. G. Montarolo P. Goelet V. F. Castellucci J. Morgan E. R. Kandel S. Schacher (1986) ArticleTitleA critical period for macromolecular synthesis in long-term heterosynaptic facilitation in Aplysia Science 234 1249–1254 Occurrence Handle3775383

    PubMed  Google Scholar 

  44. S. Schacher V. F. Castellucci E. R. Kandel (1988) ArticleTitlecAMP evokes long-term facilitation in Aplysia sensory neurons that requires new protein synthesis Science 240 1667–1669 Occurrence Handle2454509

    PubMed  Google Scholar 

  45. P. K. Dash B. Hochner E. R. Kandel (1990) ArticleTitleInjection of cAMP-responsive element into the nucleus of Aplysia sensory neurons blocks long-term facilitation Nature 345 718–721 Occurrence Handle10.1038/345718a0 Occurrence Handle2141668

    Article  PubMed  Google Scholar 

  46. B. J. Bacskai et al. (1993) ArticleTitleSpatially resolved dynamics of cAMP and protein kinase A subunits in Aplysia sensory neurons Science 260 222–226 Occurrence Handle7682336

    PubMed  Google Scholar 

  47. K. C. Martin et al. (1997) ArticleTitleMAP kinase translocates into the nucleus of the presynaptic cell and is required for long-term facilitation in Aplysia Neuron 18 899–912 Occurrence Handle10.1016/S0896-6273(00)80330-X Occurrence Handle9208858

    Article  PubMed  Google Scholar 

  48. C. H. Bailey et al. (1997) ArticleTitleMutation in the phosphorylation sites of MAP kinase blocks learningrelated internalization of apCAM in Aplysia sensory neurons Neuron 18 913–924 Occurrence Handle10.1016/S0896-6273(00)80331-1 Occurrence Handle9208859

    Article  PubMed  Google Scholar 

  49. B.-K. Kaang E. R. Kandel S. G. N. Grant (1993) ArticleTitleActivation of cAMP-responsive genes by stimuli that produce long-term facilitation in Aplysia sensory neurons Neuron 10 427–435

    Google Scholar 

  50. D. L. Glanzman E. R. Kandel S. Schacher (1990) ArticleTitleTarget-dependent structural changes accompanying long-term synaptic facilitation in Aplysia neurons Science 249 799–802 Occurrence Handle2389145

    PubMed  Google Scholar 

  51. N. Dale E. R. Kandel (1993) ArticleTitleL-glutamate may be the fast excitatory transmitter of Aplysia sensory neurons Proc. Natl. Acad. Sci. USA 90 7163–7167 Occurrence Handle8102205

    PubMed  Google Scholar 

  52. C. Alberini M. Ghirardi R. Metz E.R. Kandel (1994) ArticleTitleC_EBP is an immediate-early gene required for the consolidation of long-term facilitation in Aplysia Cell 76 1099–1114 Occurrence Handle10.1016/0092-8674(94)90386-7 Occurrence Handle8137425

    Article  PubMed  Google Scholar 

  53. D. Bartsch et al. (1995) ArticleTitleAplysia CREB2 represses long-term facilitation: relief of repression converts transient facilitation into long-term functional and structural change Cell 83 979–992 Occurrence Handle10.1016/0092-8674(95)90213-9 Occurrence Handle8521521

    Article  PubMed  Google Scholar 

  54. D. A. Bartsch Casadio K. A. Karl P. Serodio E. R. Kandel (1998) ArticleTitleCREB1 encodes a nuclear activator, a repressor, and a cytoplasmic modulator that form a regulatory unit critical for long-term facilitation Cell 95 211–223 Occurrence Handle10.1016/S0092-8674(00)81752-3 Occurrence Handle9790528

    Article  PubMed  Google Scholar 

  55. D. S. Bartsch et al. (2000) ArticleTitleEnhancement of memory-related long-term facilitation by ApAF, a novel transcription factor that acts downstream from both CREB1 and CREB2 Cell 103 595–608 Occurrence Handle10.1016/S0092-8674(00)00163-X Occurrence Handle11106730

    Article  PubMed  Google Scholar 

  56. C. H. Bailey P. Montarolo M. Chen E. R. Kandel S. Schacher (1992) ArticleTitleInhibitors of protein and RNA synthesis block structural changes that accompany long-term heterosynaptic plasticity in Aplysia Neuron 9 749–758 Occurrence Handle10.1016/0896-6273(92)90037-E Occurrence Handle1356372

    Article  PubMed  Google Scholar 

  57. C. H. Bailey M. Chen (1988) ArticleTitleLong-term memory in Aplysia modulates the total number of varicosities of single identified sensory neurons Proc. Natl. Acad. Sci. USA 85 2373–2377 Occurrence Handle3353385

    PubMed  Google Scholar 

  58. C. H. Bailey M. Chen (1989) ArticleTitleTime course of structural changes at identified sensory neuron synapses during long-term sensitization in Aplysia J. Neurosci 9 1774–1780 Occurrence Handle2723749

    PubMed  Google Scholar 

  59. C. H. Bailey E. R. Kandel (1993) ArticleTitleStructural changes accompanying memory storage Annu. Rev. Physiol 55 397–426 Occurrence Handle10.1146/annurev.ph.55.030193.002145 Occurrence Handle8466181

    Article  PubMed  Google Scholar 

  60. A. N. Hedge et al. (1997) ArticleTitleUbiquitin C-terminal hydrolase is an immediate-early gene essential for long-term facilitation in Aplysia Cell 89 115–126 Occurrence Handle10.1016/S0092-8674(00)80188-9 Occurrence Handle9094720

    Article  PubMed  Google Scholar 

  61. D. G. Chain et al. (1999) ArticleTitleMechanisms for generating the autonomous cAMP-dependent protein kinase required for long-term facilitation in Aplysia Neuron 22 147–156 Occurrence Handle10.1016/S0896-6273(00)80686-8 Occurrence Handle10027297

    Article  PubMed  Google Scholar 

  62. M. Mayford A. Barzilai F. Keller S. Schacher E. R. Kandel (1992) ArticleTitleModulation of an NCAM-related adhesion molecule with long-term synaptic plasticity in Aplysia Science 256 638–644 Occurrence Handle1585176

    PubMed  Google Scholar 

  63. C. H. Bailey M. Chen F. Keller E. R. Kandel (1992) ArticleTitleSerotonin-mediated endocytosis of apCAM: an early step of learning-related synaptic growth in Aplysia Science 256 645–649 Occurrence Handle1585177

    PubMed  Google Scholar 

  64. K. C. Martin et al. (1998) ArticleTitleSynapse-specific transcription-dependent long-term facilitation of the sensory to motor neuron connection in Aplysia: a function for local protein synthesis in memory storage Cell 91 927–938 Occurrence Handle10.1016/S0092-8674(00)80484-5

    Article  Google Scholar 

  65. A. Casadio et al. (1999) ArticleTitleA transient neuron-wide form of CREB-mediated long-term facilitation can be stabilized at specific synapses by local protein synthesis Cell 99 221–237 Occurrence Handle10.1016/S0092-8674(00)81653-0 Occurrence Handle10535740

    Article  PubMed  Google Scholar 

  66. B. J. Bacskai et al. (1993) ArticleTitleSpatially resolved dynamics of cAMP and protein kinase A subunits in Aplysia sensory neurons Science 260 222–226 Occurrence Handle7682336

    PubMed  Google Scholar 

  67. S. G. N. Grant T. J. O’Dell K. A. Karl P. L. Stein P. Soriano E. R. Kandel (1992) ArticleTitleImpaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice Science 258 1903–1910 Occurrence Handle1361685

    PubMed  Google Scholar 

  68. L. R. Squire E. R Kandel (1999) Memory: Mind to Molecules Scientific American Books New York

    Google Scholar 

  69. T. V. Bliss T. Lømo (1973) ArticleTitleLong-lasting potentiation of synaptic transmission in the denate area of the anaesthetized rabbit following stimulation of the perforant path J. Physiol 232 331–356 Occurrence Handle4727084

    PubMed  Google Scholar 

  70. R. G. M. Morris E. Anderson G. S. Lynch M. Baudry (1986) ArticleTitleSelective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5 Nature 319 774–776 Occurrence Handle10.1038/319774a0 Occurrence Handle2869411

    Article  PubMed  Google Scholar 

  71. U. Frey Y.-Y. Huang E. R. Kandel (1993) ArticleTitleEffects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons Science 260 1661–1664 Occurrence Handle8389057

    PubMed  Google Scholar 

  72. Y.-Y. Huang E. R. Kandel (1994) ArticleTitleRecruitment of long-lasting and protein kinase A-dependent long-term potentiation in the CA1 region of hippocampus requires repeated tetanization Learning & Memory 1 74–82

    Google Scholar 

  73. P. V. Nguyen T. Abel E. R. Kandel (1994) ArticleTitleRequirement of a critical period of transcription for induction of a late phase of LTP Science 265 1104–1107 Occurrence Handle8066450

    PubMed  Google Scholar 

  74. V. Y. Bolshakov H. Golan E. R. Kandel S. A. Siegelbaum (1997) ArticleTitleRecruitment of new sites of synaptic transmission during the cAMP-dependent late phase of LTP at CA3-CA1 synapses in the hippocampus Neuron 19 635–651 Occurrence Handle10.1016/S0896-6273(00)80377-3 Occurrence Handle9331354

    Article  PubMed  Google Scholar 

  75. R. C. Malenka R. A. Nicoll (1997) ArticleTitleSilent synapses speak up Neuron 19 473–476 Occurrence Handle10.1016/S0896-6273(00)80362-1 Occurrence Handle9331339

    Article  PubMed  Google Scholar 

  76. L. Ma L. Zablow E. R. Kandel S. A. Siegelbaum (1999) ArticleTitleCyclic AMP induces functional presynaptic boutons in hippocampal CA3-CA1 neuronal cultures Nature Neurosci 2 24–33 Occurrence Handle10.1038/4525 Occurrence Handle10195176

    Article  PubMed  Google Scholar 

  77. R. Bourtchouladze B. Franguelli J. Blendy D. Cioffi G. Schutz A.J. Silva (1994) ArticleTitleDeficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein Cell 79 59–68 Occurrence Handle10.1016/0092-8674(94)90400-6 Occurrence Handle7923378

    Article  PubMed  Google Scholar 

  78. S. Impey et al. (1998) ArticleTitleCross talk between ERK and PKA is required for Ca2+ stimulation of CEBdependent transcription and ERK nuclear translocation Neuron 21 869–883 Occurrence Handle10.1016/S0896-6273(00)80602-9 Occurrence Handle9808472

    Article  PubMed  Google Scholar 

  79. Y.-Y. Huang E. R. Kandel (1995) ArticleTitleD1/D5 receptor agonists induce a protein synthesis-dependent late potentiation in the CA1 region of the hippocampus Proc. Natl. Acad. Sci. USA 92 2446–2450 Occurrence Handle7708662

    PubMed  Google Scholar 

  80. D. Muller (1997) ArticleTitleUltrastructural plasticity of excitatory synapses Rev. Neurosci 8 77–93 Occurrence Handle9344180

    PubMed  Google Scholar 

  81. J. D. English J. D. Sweat (1996) ArticleTitleActivation of p42 mitogen-activated protein kinase in hippocampal long term potentiation J. Biol. Chem 271 24329–24332 Occurrence Handle10.1074/jbc.271.40.24329 Occurrence Handle8798683

    Article  PubMed  Google Scholar 

  82. F. Engert T. Bonhoeffer (1999) ArticleTitleDendritic spine changes associated with hippocampal long-term synaptic plasticity Nature 399 66–70 Occurrence Handle10.1038/19978 Occurrence Handle10331391

    Article  PubMed  Google Scholar 

  83. D. G. Winder I. M. Mansuy M. Osman T. M. Moallem E. R. Kandel (1998) ArticleTitleGenetic and pharmacological evidence for a novel, intermediate phase of long-term potentiation (I-LTP) suppressed by calcineurin Cell 92 25–37 Occurrence Handle10.1016/S0092-8674(00)80896-X Occurrence Handle9489697

    Article  PubMed  Google Scholar 

  84. T. Abel et al. (1997) ArticleTitleGenetic demonstration of a role for PKA in the last phase of LTP and in hippocampus-based long-term memory Cell 88 615–626 Occurrence Handle10.1016/S0092-8674(00)81904-2 Occurrence Handle9054501

    Article  PubMed  Google Scholar 

  85. J. O’Keefe L Nadel (1978) The Hippocampus as a Cognitive Map Clarendon Press, Oxford

    Google Scholar 

  86. A. Rotenberg M. Mayford R. D. Hawkins E. R. Kandel R. U. Muller (1996) ArticleTitleMice expressing activated CaMKII lack low frequency LTP and do not form stable place cells in the CA1 region of the hippocampus Cell 87 1351–1361 Occurrence Handle10.1016/S0092-8674(00)81829-2 Occurrence Handle8980240

    Article  PubMed  Google Scholar 

  87. C. Kentros E. Hargreaves R. D. Hawkins E. R. Kandel M. Shapiro R. U. Muller (1998) ArticleTitleAbolition of long-term stability of new hippocampal place cell maps by NMDA receptor blockade Science 280 2121–2126 Occurrence Handle10.1126/science.280.5372.2121 Occurrence Handle9641919

    Article  PubMed  Google Scholar 

  88. A. Rotenberg T. Abel R. D. Hawkins E. R. Kandel R. U. Muller (2000) ArticleTitleParallel instabilities of long-term potentiation, place cells, and learning causes by decreased protein kinase A activity J. Neurosci 20 8096–8102 Occurrence Handle11050131

    PubMed  Google Scholar 

  89. Agnihotri, N., Hawkins, R. D., Kandel E. R., and Kentros C. (2001) Protein synthesis inhibition selectively abolishes long-term stability of hippocampal place cell maps. Soc. Neurosci. Abstr., in press

  90. Kentros, C., Agnihotri, N., Hawkins, R., Muller, R., and Kandel, E. (2001) Stabilization of the hippocampal representation of space in mice requires attention. Soc. Neurosci. Abstr., in press

  91. I. M. Mansuy M. Mayford B. Jacob E. R. Kandel M. E. Bach (1990) ArticleTitleRestricted and regulated overexpression reveals calcineurin as a key component in the transition from short-term to long-term memory Cell 92 39–49 Occurrence Handle10.1016/S0092-8674(00)80897-1

    Article  Google Scholar 

  92. G. Mallaret et al. (2001) ArticleTitleInducible and reversible enhancement of learning, memory, and long-term potentiation by genetic inhibition of calcineurin Cell 104 675–686 Occurrence Handle11257222

    PubMed  Google Scholar 

  93. U. Frey R. G. Morris (1997) ArticleTitleSynaptic tagging and long-term potentiation Nature 385 533–536 Occurrence Handle10.1038/385533a0 Occurrence Handle9020359

    Article  PubMed  Google Scholar 

  94. V. F. Castellucci T. J. Carew E. R. Kandel (1978) ArticleTitleCellular analysis of long-term habituation of the gill-withdrawal reflex in Aplysia Science 202 1306–1308 Occurrence Handle214854

    PubMed  Google Scholar 

  95. B. Milner L. R. Squire E. R. Kandel (1998) ArticleTitleCognitive neuroscience and the study of memory Neuron 20 445–468 Occurrence Handle10.1016/S0896-6273(00)80987-3 Occurrence Handle9539121

    Article  PubMed  Google Scholar 

  96. L. R. Squire S. Zola-Morgan (1991) ArticleTitleThe medial temporal lobe memory system Science 253 1380–1386 Occurrence Handle1896849

    PubMed  Google Scholar 

  97. J. Dubnau T. Tully (1998) ArticleTitleGene discovery in Drosophila: New insights for learning and memory Annu. Rev. Neurosci 21 407–444 Occurrence Handle10.1146/annurev.neuro.21.1.407 Occurrence Handle9530502

    Article  PubMed  Google Scholar 

  98. W. N. Frost V. F. Castellucci R. D. Hawkins E. R. Kandel (1985) ArticleTitleMonosynaptic connections made by the sensory neurons of the gill- and siphon-withdrawal reflex in Aplysia participate in the storage of long-term memory for sensitization Proc. Natl. Acad. Sci. USA 82 8266–8269

    Google Scholar 

  99. K. C. Martin M. Barad E. R. Kandel (2000) ArticleTitleLocal protein synthesis and its role in synapse specific plasticity Curr. Opin. Neurobiol 10 587–592

    Google Scholar 

  100. E. M. Schuman (1997) ArticleTitleSynapse specificity and long-term information storage Neuron 18 339–342 Occurrence Handle10.1016/S0896-6273(00)81234-9 Occurrence Handle9115727

    Article  PubMed  Google Scholar 

  101. O. Steward (1997) ArticleTitlemRNA localization in neurons: a multipurpose mechanism? Neuron 18 9–12 Occurrence Handle10.1016/S0896-6273(01)80041-6 Occurrence Handle9010200

    Article  PubMed  Google Scholar 

  102. J. Weiner (1999) Time Love, Memory: A Great Biologist and His Quest for the Origins of Behavior Knopf New York

    Google Scholar 

  103. R. Muller (1996) ArticleTitleA quarter of a century of place cells Neuron 17 813–822 Occurrence Handle10.1016/S0896-6273(00)80214-7 Occurrence Handle8938115

    Article  PubMed  Google Scholar 

  104. T. J. McHugh K. I. Blum J. Z. Tsein S. Tonegawa M. A. Wilson (1996) ArticleTitleImpaired hippocampal representation of space in CA1 specific NMDAR1 knockout mice Cell 87 1339–1349 Occurrence Handle10.1016/S0092-8674(00)81828-0 Occurrence Handle8980239

    Article  PubMed  Google Scholar 

  105. V. Y. Bolshakov S. A. Siegelbaum (1995) ArticleTitleRegulation of hippocampal transmitter release during development and long-term potentiation Science 269 1730–1734 Occurrence Handle7569903

    PubMed  Google Scholar 

  106. C. F. Stevens Y. Wang (1994) ArticleTitleChanges in reliability of synaptic function as a mechanism for plasticity Nature 371 704–707 Occurrence Handle10.1038/371704a0 Occurrence Handle7935816

    Article  PubMed  Google Scholar 

  107. Ebbinghaus, H. (1885) Memory: A Contribution to Experimental Psychology Reprinted, Dover: New York, 1963

  108. L. B. Flexner J. B. Flexner (1966) ArticleTitleEffect of acetoxycyclohexamide and of an acetoxycyclohexamide-purymycin mixture on cerebral protein synthesis and memory in mice Proc. Natl. Acad. Sci. USA 55 369–374 Occurrence Handle5220953

    PubMed  Google Scholar 

  109. J. J. Brink R. E. Davis B. W. Agranoff (1966) ArticleTitleEffects of puromycin, acetoxycyclohexamide and actinomycin D on protein synthesis in goldfish brain J. Neurochem 13 889–896 Occurrence Handle5927758

    PubMed  Google Scholar 

  110. P. Fatt B. Katz (1951) ArticleTitleAn analysis of the end-plate potential recorded with an intracellular electrode J. Physiol. (Lond.) 115 320–370

    Google Scholar 

  111. P. Greengard (1976) ArticleTitlePossible role for cyclic nucleotides and phosphorylated membrane proteins in postsynaptic actions of neurotransmitters Nature 260 101–108 Occurrence Handle10.1038/260101a0 Occurrence Handle176592

    Article  PubMed  Google Scholar 

  112. S. L. Monsour K. R. Thomas M. R. Capecchi (1988) ArticleTitleDisruption of the proto-oncogene int-2 in mouse embryonic-derived stem cells: a general strategy for targeting mutations to nonselectible genes Nature 336 348–352 Occurrence Handle10.1038/336348a0 Occurrence Handle3194019

    Article  PubMed  Google Scholar 

  113. L. H. Reid E. G. Shesely H. S. Kin O. Smithies (1991) ArticleTitleCotransformation and gene targeting in mouse embryonic stem cells Mol. Cell Biol 11 2769–2777 Occurrence Handle1850104

    PubMed  Google Scholar 

  114. B. H. Koller O. Smithies (1989) ArticleTitleInactivating the beta 2-microglobulin locus in mouse embryonic stem cells by homoglous recombination Proc. Natl. Acad. Sci. USA 86 8932–8935 Occurrence Handle2682666

    PubMed  Google Scholar 

  115. E. R. Kandel J. H. Schwartz (1982) ArticleTitleMolecular biology of learning: Modulation of transmitter release Science 218 433–443 Occurrence Handle6289442

    PubMed  Google Scholar 

  116. R. D. Blitzer et al. (1982) ArticleTitleGaMKII by cAMP-regulated protein phosphatase activity during LTP. Science 280 1940–1942 Occurrence Handle10.1126/science.280.5371.1940

    Article  Google Scholar 

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  1. College of Physicians and Surgeons, Columbia University, 722 West 168 Street, NY, 10032, New York, USA

    Eric R. Kandel

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Kandel, E.R. The Molecular Biology of Memory Storage: A Dialog Between Genes and Synapses. Biosci Rep 24, 475–522 (2004). https://doi.org/10.1007/s10540-005-2742-7

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