Skip to main content
SpringerLink
Log in

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

  • Published:
Bioscience Reports

Abstract

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

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  4. Kupfermann, I. And Kandel, E. R. (1969) Neuronal controls of a behavioral response mediated by the abdominal ganglion of Aplysia. Science 164: 847–850.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  10. Frost, W. N., Castellucci, V. F., Hawkins, R. D., and Kandel, E. R. (1985) Monosynaptic 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. Byrne, J., Castellucci, V., and Kandel, E. R. (1974) Receptive fields and response properties of mechanoreceptor neurons innervating skin and mantle shelf of Aplysia. J. Neurophysiol. 37: 1041–1064.

    Google Scholar 

  12. Castellucci, V. F., Blumenfeld, H., Goelet, P., and Kandel, E. R. (1989) Inhibitor of protein synthesis blocks long-term behavioral sensitization in the isolated gill-withdrawal reflex of Aplysia. J. Neurobiol. 20: 1–9.

    Google Scholar 

  13. Kandel, E. R. (1976) Cellular Basis of Behaûior: An Introduction to Behaûioral Biology. Freeman: San Francisco.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  17. Kandel, E. R. and Spencer, W. A. (1968) Cellular neurophysiological approaches in the study of learning. Physiol. Reû. 48: 65–134.

    Google Scholar 

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

    Google Scholar 

  19. Hawkins, R. D., Castellucci, V. F., and Kandel, E. R. (1981) Interneurons 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.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  23. Carew, T. J., Castellucci, V. F., and Kandel, E. R. (1979) Sensitization in Aplysia: Restoration of transmission in synapses inactivated by long-term habituation. Science 205: 417–419.

    Google Scholar 

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

    Google Scholar 

  25. Klein, M., Hochner, B., and Kandel, E. R. (1986) Facilitatory 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. Schwartz, J. H., Castellucci, V. F., and Kandel, E. R. (1971) Functioning of identified neurons and synapses in abdominal ganglion of Aplysia in absence of protein synthesis. J. Neurophysiol. 34: 939–953.

    Google Scholar 

  27. Cedar, H., Kandel, E. R., and Schwartz, J. H. (1972) Cyclic adenosine monophosphate in the nervous system of Aplysia californica. I. Increased synthesis in response to synaptic stimulation. J. Gen. Physiol. 60: 558–569.

    Google Scholar 

  28. Kriegstein, A. R., Castellucci, V., and Kandel, E. R. (1974) Metamorphosis of Aplysia californica in laboratory culture. Proc. Natl. Acad. Sci. USA 71: 3654–3658.

    Google Scholar 

  29. Cedar, H. and Schwartz, J. H. (1972) Cyclic adenosine monophosphate in the nervous system of Aplysia california. II. Effect of serotonin and dopamine. J. Gen. Physiol. 60: 570–587.

    Google Scholar 

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

    Google Scholar 

  31. Castellucci, V. and Kandel, E. R. (1976) Presynaptic facilitation as a mechanism for behavioral sensitization in Aplysia. Science 194: 1176–1178.

    Google Scholar 

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

    Google Scholar 

  33. Kandel, E. R., Brunelli, M., Byrne, J., and Castellucci, V. (1976) A 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.

    Google Scholar 

  34. Glanzman, D. L., Mackey, S. L., Hawkins, R. D., Dyke, A. M., Lloyd, P. E., and Kandel, E. R. (1989) Depletion 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.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  37. Castellucci, V. F., Kandel, E. R., Schwartz, J. H., Wilson, F. D., Nairn, A. C., and Greengard, P. (1980) Intracellular 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.

    Google Scholar 

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

    Google Scholar 

  39. Siegelbaum, S., Camardo, J. S., and Kandel, E. R. (1982) Serotonin and cAMP close single K??channels in Aplysia sensory neurons. Nature 299: 413–417.

    Google Scholar 

  40. Shuster, M. J., Camardo, J. S., Siegelbaum, S. A., and Kandel, E. R. (1985) Cyclic AMP-dependent protein kinase closes the serotonin-sensitive K?channels of Aplysia sensory neurons in cell-free membrane patches. Nature 313: 392–395.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  45. Dash, P. K., Hochner, B., and Kandel, E. R. (1990) Injection of cAMP-responsive element into the nucleus of Aplysia sensory neurons blocks long-term facilitation. Nature 345: 718–721.

    Google Scholar 

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

    Google Scholar 

  47. Martin, K. C. et al. (1997) MAP kinase translocates into the nucleus of the presynaptic cell and is required for long-term facilitation in Aplysia. Neuron 18: 899–912.

    Google Scholar 

  48. Bailey, C. H. et al. (1997) Mutation in the phosphorylation sites of MAP kinase blocks learningrelated internalization of apCAM in Aplysia sensory neurons. Neuron 18: 913–924.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  52. Alberini, C., Ghirardi, M., Metz, R., and Kandel, E. R. (1994) C_EBP is an immediate-early gene required for the consolidation of long-term facilitation in Aplysia. Cell 76: 1099–1114.

    Google Scholar 

  53. Bartsch, D., et al. (1995) Aplysia CREB2 represses long-term facilitation: Relief of repression converts transient facilitation into long-term functional and structural change. Cell 83: 979–992.

    Google Scholar 

  54. Bartsch, D. Casadio, A., Karl, K. A., Serodio, P., and Kandel, E. R. (1998) CREB1 encodes a nuclear activator, a repressor, and a cytoplasmic modulator that form a regulatory unit critical for long-term facilitation. Cell 95: 211–223.

    Google Scholar 

  55. Bartsch, D. et al. (2000) Enhancement of memory-related long-term facilitation by ApAF, a novel transcription factor that acts downstream from both CREB1 and CREB2. Cell 103: 595–608.

    Google Scholar 

  56. Bailey, C. H., Montarolo, P., Chen, M., Kandel, E. R., and Schacher, S. (1992) Inhibitors of protein and RNA synthesis block structural changes that accompany long-term heterosynaptic plasticity in Aplysia. Neuron 9: 749–758.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  59. Bailey, C. H. and Kandel, E. R. (1993) Structural changes accompanying memory storage. Annu. Reû. Physiol. 55: 397–426.

    Google Scholar 

  60. Hedge, A. N. et al. (1997) Ubiquitin C-terminal hydrolase is an immediate-early gene essential for long-term facilitation in Aplysia. Cell 89: 115–126.

    Google Scholar 

  61. Chain, D. G. et al. (1999) Mechanisms for generating the autonomous cAMP-dependent protein kinase required for long-term facilitation in Aplysia. Neuron 22: 147–156.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  64. Martin, K. C. et al. (1998) Synapse-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.

    Google Scholar 

  65. Casadio, A. et al. (1999) A transient neuron-wide form of CREB-mediated long-term facilitation can be stabilized at specific synapses by local protein synthesis. Cell 99: 221–237.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  70. Morris, R. G. M., Anderson, E., Lynch, G. S., and Baudry, M. (1986) Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature 319: 774–776.

    Google Scholar 

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

    Google Scholar 

  72. Huang, Y.-Y. and Kandel, E. R. (1994) Recruitment 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. Nguyen, P. V., Abel, T., and Kandel, E. R. (1994) Requirement of a critical period of transcription for induction of a late phase of LTP. Science 265: 1104–1107.

    Google Scholar 

  74. Bolshakov, V. Y., Golan, H., Kandel, E. R., and Siegelbaum, S. A. (1997) Recruitment 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.

    Google Scholar 

  75. Malenka, R. C. and Nicoll, R. A. (1997) Silent synapses speak up. Neuron 19: 473–476.

    Google Scholar 

  76. Ma, L., Zablow, L., Kandel, E. R., and Siegelbaum, S. A. (1999) Cyclic AMP induces functional presynaptic boutons in hippocampal CA3-CA1 neuronal cultures. Nature Neurosci. 2: 24–3.

    Google Scholar 

  77. Bourtchouladze, R., Franguelli, B., Blendy, J., Cioffi, D., Schutz, G., and Silva, A. J. (1994) Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79: 59–68.

    Google Scholar 

  78. Impey, S. et al. (1998) Cross talk between ERK and PKA is required for Ca2C stimulation of CEBdependent transcription and ERK nuclear translocation. Neuron 21: 869–883.

    Google Scholar 

  79. Huang, Y.-Y. and Kandel, E. R. (1995) D1_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.

    Google Scholar 

  80. Muller, D. (1997) Ultrastructural plasticity of excitatory synapses. Reû. Neurosci. 8: 77–93.

    Google Scholar 

  81. English, J. D. and Sweat, J. D. (1996) Activation of p42 mitogen-activated protein kinase in hippocampal long term potentiation. J. Biol. Chem. 271: 24329–24332.

    Google Scholar 

  82. Engert, F. and Bonhoeffer, T. (1999) Dendritic spine changes associated with hippocampal long-term synaptic plasticity. Nature 399: 66–70.

    Google Scholar 

  83. Winder, D. G., Mansuy, I. M., Osman, M., Moallem, T. M., and Kandel, E. R. (1998) Genetic and pharmacological evidence for a novel, intermediate phase of long-term potentiation (I-LTP) suppressed by calcineurin. Cell 92: 25–37.

    Google Scholar 

  84. Abel, T. et al. (1997) Genetic demonstration of a role for PKA in the last phase of LTP and in hippocampus-based long-term memory. Cell 88: 615–626.

    Google Scholar 

  85. O'Keefe, J. and Nadel, L. (1978) The Hippocampus as a Cognitiûe Map. Clarendon Press: Oxford.

    Google Scholar 

  86. Rotenberg, A., Mayford, M., Hawkins, R. D., Kandel, E. R., and Muller, R. U. (1996) Mice 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.

    Google Scholar 

  87. Kentros, C., Hargreaves, E., Hawkins, R. D., Kandel, E. R., Shapiro, M., and Muller, R. U. (1998) Abolition of long-term stability of new hippocampal place cell maps by NMDA receptor blockade. Science 280: 2121–2126.

    Google Scholar 

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

    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. Mansuy, I. M., Mayford, M., Jacob, B., Kandel, E. R., and Bach, M. E. (1990) Restricted and regulated overexpression reveals calcineurin as a key component in the transition from short-term to long-term memory. Cell 92: 39–49.

    Google Scholar 

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

    Google Scholar 

  93. Frey, U. and Morris, R. G. (1997) Synaptic tagging and long-term potentiation. Nature 385: 533–536.

    Google Scholar 

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

    Google Scholar 

  95. Milner, B. Squire, L. R., and Kandel, E. R. (1998) Cognitive neuroscience and the study of memory. Neuron 20: 445–468.

    Google Scholar 

  96. Squire, L. R. and Zola-Morgan, S. (1991) The medial temporal lobe memory system. Science 253: 1380–1386.

    Google Scholar 

  97. Dubnau, J. and Tully, T. (1998) Gene discovery in Drosophila: New insights for learning and memory. Annu. Reû. Neurosci. 21: 407–444.

    Google Scholar 

  98. Frost, W. N., Castellucci, V. F., Hawkins, R. D., and Kandel, E. R. (1985) Monosynaptic 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. Martin, K. C., Barad, M., and Kandel, E. R. (2000) Local protein synthesis and its role in synapsespecific plasticity. Curr. Opin. Neurobiol. 10: 587–592.

    Google Scholar 

  100. Schuman, E. M. (1997) Synapse specificity and long-term information storage. Neuron 18: 339–342.

    Google Scholar 

  101. Steward, O. (1997) mRNA localization in neurons: A multipurpose mechanism? Neuron 18: 9–12.

    Google Scholar 

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

    Google Scholar 

  103. Muller, R. (1996) A quarter of a century of place cells. Neuron 17: 813–822.

    Google Scholar 

  104. McHugh, T. J., Blum, K. I., Tsein, J. Z., Tonegawa, S., and Wilson, M. A. (1996) Impaired hippocampal representation of space in CA1 specific NMDAR1 knockout mice. Cell 87: 1339–1349.

    Google Scholar 

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

    Google Scholar 

  106. Stevens, C. F. and Wang, Y. (1994) Changes in reliability of synaptic function as a mechanism for plasticity. Nature 371: 704–707.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  111. Greengard, P. (1976) Possible role for cyclic nucleotides and phosphorylated membrane proteins in postsynaptic actions of neurotransmitters. Nature 260: 101–108.

    Google Scholar 

  112. Monsour, S. L., Thomas, K. R., and Capecchi, M. R. (1988) Disruption 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.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  115. Kandel, E. R. and Schwartz, J. H. (1982) Molecular biology of learning: Modulation of transmitter release. Science 218: 433–443.

    Google Scholar 

  116. Blitzer, R. D. et al. (1998) Gating of CaMKII by cAMP-regulated protein phosphatase activity during LTP. Science 280: 1940–1942.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Physicians and Surgeons, Columbia University, New York, New York, USA

    Eric R. Kandel

Authors
  1. Eric R. Kandel
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kandel, E.R. NOBEL LECTURE: The Molecular Biology of Memory Storage: A Dialog Between Genes and Synapses. Biosci Rep 21, 565–611 (2001). https://doi.org/10.1023/A:1014775008533

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1014775008533

Search

Navigation