Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The BCM theory of synapse modification at 30: interaction of theory with experiment

Nature Reviews Neuroscience volume 13, pages 798–810 (2012)Cite this article

Subjects

Abstract

Thirty years have passed since the publication of Elie Bienenstock, Leon Cooper and Paul Munro's 'Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex', known as the BCM theory of synaptic plasticity. This theory has guided experimentalists to discover some fundamental properties of synaptic plasticity and has provided a mathematical structure that bridges molecular mechanisms and systems-level consequences of learning and memory storage.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Information transfer in cortical cells and theories of synaptic modification.
Figure 2: Ocular dominance plasticity in the kitten visual cortex.
Figure 3: Results of BCM simulations in environments using noisy natural images.
Figure 4: Activity patterns that trigger ocular dominance plasticity.
Figure 5: Experimental verification of the φ function and the sliding modification threshold.
Figure 6: Choreography of the ocular dominance shift in the mouse visual cortex.

References

  1. Bienenstock, E. L., Cooper, L. N. & Munro, P. W. Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex. J. Neurosci. 2, 32–48 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. von der Malsburg, C. Self-organization of orientation sensitive cells in the striate cortex. Kybernetik 14, 85–100 (1973).

    Article  CAS  PubMed  Google Scholar 

  3. Nass, M. M. & Cooper, L. N. A theory for the development of feature detecting cells in visual cortex. Biol. Cybern. 19, 1–18 (1975).

    Article  CAS  PubMed  Google Scholar 

  4. Cooper, L. N., Liberman, F. & Oja, E. A theory for the acquisition and loss of neuron specificity in visual cortex. Biol. Cybern. 33, 9–28 (1979).

    Article  CAS  PubMed  Google Scholar 

  5. Hebb, D. O. The Organization of Behavior: A Neuropsychological Theory (Wiley, 1949).

    Google Scholar 

  6. Lowel, S. & Singer, W. Selection of intrinsic horizontal connections in the visual cortex by correlated neuronal activity. Science 255, 209–212 (1992).

    Article  CAS  PubMed  Google Scholar 

  7. Shatz, C. J. The developing brain. Sci. Am. 267, 60–67 (1992).

    Article  CAS  PubMed  Google Scholar 

  8. Cooper, L. N. in Proceedings of the Nobel Symposium on Collective Properties of Physical Systems (eds Lundqvist, B., Lundqvist, S. & Runnstrom-Reio, V.) 252–264 (Aspen Garden: Nobel, 1973).

    Book  Google Scholar 

  9. Hubel, D. H. & Wiesel, T. N. Receptive fields, binocular interaction and functional architecture in the cat's visual cortex. J. Physiol. 160, 106–154 (1962).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wiesel, T. N. & Hubel, D. H. Single-cell responses in striate cortex of kittens deprived of vision in one eye. J. Neurophysiol. 26, 1003–1017 (1963).

    Article  CAS  PubMed  Google Scholar 

  11. Mioche, L. & Singer, W. Chronic recordings from single sites of kitten striate cortex during experience-dependent modifications of receptive-field properties. J. Neurophysiol. 62, 185–197 (1989).

    Article  CAS  PubMed  Google Scholar 

  12. Intrator, N. & Cooper, L. N. Objective function formulation of the BCM theory of visual cortical plasticity: statistical connections, stability conditions. Neural Networks 5, 3–17 (1992).

    Article  Google Scholar 

  13. Clothiaux, E. E., Bear, M. F. & Cooper, L. N. Synaptic plasticity in visual cortex: comparison of theory with experiment. J. Neurophysiol. 66, 1785–1804 (1991).

    Article  CAS  PubMed  Google Scholar 

  14. Blais, B. S., Intrator, N., Shouval, H. Z. & Cooper, L. N. Receptive field formation in natural scene environments. comparison of single-cell learning rules. Neural Comput. 10, 1797–1813 (1998).

    Article  CAS  PubMed  Google Scholar 

  15. Blais, B. S., Shouval, H. Z. & Cooper, L. N. The role of presynaptic activity in monocular deprivation: comparison of homosynaptic and heterosynaptic mechanisms. Proc. Natl Acad. Sci. USA 96, 1083–1087 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Blais, B., Cooper, L. N. & Shouval, H. Formation of direction selectivity in natural scene environments. Neural Comput. 12, 1057–1066 (2000).

    Article  CAS  PubMed  Google Scholar 

  17. Blais, B. S. et al. Recovery from monocular deprivation using binocular deprivation. J. Neurophysiol. 100, 2217–2224 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Frenkel, M. Y. & Bear, M. F. How monocular deprivation shifts ocular dominance in visual cortex of young mice. Neuron 44, 917–923 (2004).

    Article  CAS  PubMed  Google Scholar 

  19. Katz, L. C. & Shatz, C. J. Synaptic activity and the construction of cortical circuits. Science 274, 1133–1138 (1996).

    Article  CAS  PubMed  Google Scholar 

  20. Ramoa, A. S., Paradiso, M. A. & Freeman, R. D. Blockade of intracortical inhibition in kitten striate cortex: effects on receptive field properties and associated loss of ocular dominance plasticity. Exp. Brain Res. 73, 285–296 (1988).

    Article  CAS  PubMed  Google Scholar 

  21. Cruikshank, S. J. & Weinberger, N. M. Receptive-field plasticity in the adult auditory cortex induced by Hebbian covariance. J. Neurosci. 16, 861–875 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Fregnac, Y. & Shulz, D. E. Activity-dependent regulation of receptive field properties of cat area 17 by supervised Hebbian learning. J. Neurobiol. 41, 69–82 (1999).

    Article  CAS  PubMed  Google Scholar 

  23. Abraham, W. C., Logan, B., Wolff, A. & Benuskova, L. “Heterosynaptic” LTD in the dentate gyrus of anesthetized rat requires homosynaptic activity. J. Neurophysiol. 98, 1048–1051 (2007).

    Article  PubMed  Google Scholar 

  24. Newman, E. L. & Norman, K. A. Moderate excitation leads to weakening of perceptual representations. Cereb. Cortex 20, 2760–2770 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Rittenhouse, C. D., Shouval, H. Z., Paradiso, M. A. & Bear, M. F. Monocular deprivation induces homosynaptic long-term depression in visual cortex. Nature 397, 347–350 (1999).

    Article  CAS  PubMed  Google Scholar 

  26. Coleman, J. E. et al. Rapid structural remodeling of thalamocortical synapses parallels experience-dependent functional plasticity in mouse primary visual cortex. J. Neurosci. 30, 9670–9682 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rittenhouse, C. D. et al. Stimulus for rapid ocular dominance plasticity in visual cortex. J. Neurophysiol. 95, 2947–2950 (2006).

    Article  PubMed  Google Scholar 

  28. Linden, M. L., Heynen, A. J., Haslinger, R. H. & Bear, M. F. Thalamic activity that drives visual cortical plasticity. Nature Neurosci. 12, 390–392 (2009).

    Article  CAS  PubMed  Google Scholar 

  29. Blais, B. S., Cooper, L. N. & Shouval, H. Z. Effect of correlated lateral geniculate nucleus firing rates on predictions for monocular eye closure versus monocular retinal inactivation. Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 80, 061915 (2009).

    Article  CAS  PubMed  Google Scholar 

  30. Bear, M. F. Bidirectional synaptic plasticity: from theory to reality. Phil. Trans. R. Soc. Lond. B. 358, 649–655 (2003).

    Article  Google Scholar 

  31. Wiesel, T. N. & Hubel, D. H. Comparison of the effects of unilateral and bilateral eye closure on cortical unit responses in kittens. J. Neurophysiol. 28, 1029–1040 (1965).

    Article  CAS  PubMed  Google Scholar 

  32. Stent, G. S. A physiological mechanism for Hebb's postulate of learning. Proc. Natl Acad. Sci. USA 70, 997–1001 (1973).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Oja, E. A. A simplified neuron model as a principal component analyzer. J. Math. Biol. 15, 267–273 (1982).

    Article  CAS  PubMed  Google Scholar 

  34. Kind, P. C. Cortical plasticity: is it time for a change? Curr. Biol. 9, R640–R643 (1999).

    Article  CAS  PubMed  Google Scholar 

  35. McNaughton, B. L., Douglas, R. M. & Goddard, G. V. Synaptic enhancement in fascia dentata: cooperativity among coactive afferents. Brain Res. 157, 277–293 (1978).

    Article  CAS  PubMed  Google Scholar 

  36. Kelso, S. R., Ganong, A. H. & Brown, T. H. Hebbian synapses in hippocampus. Proc. Natl Acad. Sci. USA 83, 5326–5330 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Dudek, S. M. & Bear, M. F. Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade. Proc. Natl Acad. Sci. USA 89, 4363–4367 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Stevens, C. F. Neurobiology. A depression long awaited. Nature 347, 16 (1990).

    Article  CAS  PubMed  Google Scholar 

  39. Stevens, C. F. Going down the way you came up. Curr. Biol. 3, 891–892 (1993).

    Article  CAS  PubMed  Google Scholar 

  40. Stevens, C. F. Strengths and weaknesses in memory. Nature 381, 471–472 (1996).

    Article  CAS  PubMed  Google Scholar 

  41. Ezzell, C. Neuroscientists manic about long-term depression studies. J. NIH Res. 5, 27–29 (1993).

    Google Scholar 

  42. Malenka, R. C. & Bear, M. F. LTP and LTD: an embarrassment of riches. Neuron 44, 5–21 (2004).

    Article  CAS  PubMed  Google Scholar 

  43. O'Connor, D. H., Wittenberg, G. M. & Wang, S. S. Graded bidirectional synaptic plasticity is composed of switch-like unitary events. Proc. Natl Acad. Sci. USA 102, 9679–9684 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Luscher, C. & Huber, K. M. Group 1 mGluR-dependent synaptic long-term depression: mechanisms and implications for circuitry and disease. Neuron 65, 445–459 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bear, M. F., Cooper, L. N. & Ebner, F. F. A physiological basis for a theory of synapse modification. Science 237, 42–48 (1987).

    Article  CAS  PubMed  Google Scholar 

  46. Lisman, J. A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory. Proc. Natl Acad. Sci. USA 86, 9574–9578 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Mulkey, R. M. & Malenka, R. C. Mechanisms underlying induction of homosynaptic long-term depression in area CA1 of the hippocampus. Neuron 9, 967–975 (1992).

    Article  CAS  PubMed  Google Scholar 

  48. Mulkey, R. M., Endo, S., Shenolikar, S. & Malenka, R. C. Involvement of a calcineurin/inhibitor-1 phosphatase cascade in hippocampal long-term depression. Nature 369, 486–488 (1994).

    Article  CAS  PubMed  Google Scholar 

  49. Cummings, J. A., Mulkey, R. M., Nicoll, R. A. & Malenka, R. C. Ca2+ signaling requirements for long-term depression in the hippocampus. Neuron 16, 825–833 (1996).

    Article  CAS  PubMed  Google Scholar 

  50. Yang, S. N., Tang, Y. G. & Zucker, R. S. Selective induction of LTP and LTD by postsynaptic [Ca2+]i elevation. J. Neurophysiol. 81, 781–787 (1999).

    Article  CAS  PubMed  Google Scholar 

  51. Dudek, S. M. & Bear, M. F. Bidirectional long-term modification of synaptic effectiveness in the adult and immature hippocampus. J. Neurosci. 13, 2910–2918 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Heynen, A. J., Abraham, W. C. & Bear, M. F. Bidirectional modification of CA1 synapses in the adult hippocampus in vivo. Nature 381, 163–166 (1996).

    Article  CAS  PubMed  Google Scholar 

  53. Bear, M. F. A synaptic basis for memory storage in the cerebral cortex. Proc. Natl Acad. Sci. USA 93, 13453–13459 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Debanne, D. & Thompson, S. M. Associative long-term depression in the hippocampus in vitro. Hippocampus 6, 9–16 (1996).

    Article  CAS  PubMed  Google Scholar 

  55. Ngezahayo, A., Schachner, M. & Artola, A. Synaptic activity modulates the induction of bidirectional synaptic changes in adult mouse hippocampus. J. Neurosci. 20, 2451–2458 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Huang, S. et al. Pull-push neuromodulation of LTP and LTD enables bidirectional experience-induced synaptic scaling in visual cortex. Neuron 73, 497–510 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Philpot, B. D., Espinosa, J. S. & Bear, M. F. Evidence for altered NMDA receptor function as a basis for metaplasticity in visual cortex. J. Neurosci. 23, 5583–5588 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Kirkwood, A., Dudek, S. M., Gold, J. T., Aizenman, C. D. & Bear, M. F. Common forms of synaptic plasticity in the hippocampus and neocortex in vitro. Science 260, 1518–1521 (1993).

    Article  CAS  PubMed  Google Scholar 

  59. Chen, W. R. et al. Long-term modifications of synaptic efficacy in the human inferior and middle temporal cortex. Proc. Natl Acad. Sci. USA 93, 8011–8015 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Massey, P. V. & Bashir, Z. I. Long-term depression: multiple forms and implications for brain function. Trends Neurosci. 30, 176–184 (2007).

    Article  CAS  PubMed  Google Scholar 

  61. Nelson, S. B. & Turrigiano, G. G. Strength through diversity. Neuron 60, 477–482 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bear, M. F. in Mechanistic Relationships Between Development and Learning (eds Carew, T. J., Menzel, R. & Shatz, C. J.) 205–225 (John Wiley and Sons, 1998).

    Google Scholar 

  63. Heynen, A. J., Quinlan, E. M., Bae, D. C. & Bear, M. F. Bidirectional, activity-dependent regulation of glutamate receptors in the adult hippocampus in vivo. Neuron 28, 527–536 (2000).

    Article  CAS  PubMed  Google Scholar 

  64. Kauer, J. A. & Malenka, R. C. Synaptic plasticity and addiction. Nature Rev. Neurosci. 8, 844–858 (2007).

    Article  CAS  Google Scholar 

  65. Bagetta, V., Ghiglieri, V., Sgobio, C., Calabresi, P. & Picconi, B. Synaptic dysfunction in Parkinson's disease. Biochem. Soc. Trans. 38, 493–497 (2010).

    Article  CAS  PubMed  Google Scholar 

  66. Koffie, R. M., Hyman, B. T. & Spires-Jones, T. L. Alzheimer's disease: synapses gone cold. Mol. Neurodegener. 6, 63 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Krueger, D. D. & Bear, M. F. Toward fulfilling the promise of molecular medicine in fragile X syndrome. Annu. Rev. Med. 62, 411–429 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Auerbach, B. D., Osterweil, E. K. & Bear, M. F. Mutations causing syndromic autism define an axis of synaptic pathophysiology. Nature 480, 63–68 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Heynen, A. J. et al. Molecular mechanism for loss of visual cortical responsiveness following brief monocular deprivation. Nature Neurosci. 6, 854–862 (2003).

    Article  CAS  PubMed  Google Scholar 

  70. Crozier, R. A., Wang, Y., Liu, C. H. & Bear, M. F. Deprivation-induced synaptic depression by distinct mechanisms in different layers of mouse visual cortex. Proc. Natl Acad. Sci. USA 104, 1383–1388 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Yoon, B. J., Smith, G. B., Heynen, A. J., Neve, R. L. & Bear, M. F. Essential role for a long-term depression mechanism in ocular dominance plasticity. Proc. Natl Acad. Sci. USA 106, 9860–9865 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Khibnik, L. A., Cho, K. K. & Bear, M. F. Relative contribution of feedforward excitatory connections to expression of ocular dominance plasticity in layer 4 of visual cortex. Neuron 66, 493–500 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Hubel, D. H., Wiesel, T. N. & LeVay, S. Plasticity of ocular dominance columns in monkey striate cortex. Phil. Trans. R. Soc. Lond. B 278, 377–409 (1977).

    Article  CAS  Google Scholar 

  74. Kleinschmidt, A., Bear, M. F. & Singer, W. Blockade of “NMDA” receptors disrupts experience-dependent plasticity of kitten striate cortex. Science 238, 355–358 (1987).

    Article  CAS  PubMed  Google Scholar 

  75. Bear, M. F., Kleinschmidt, A., Gu, Q. A. & Singer, W. Disruption of experience-dependent synaptic modifications in striate cortex by infusion of an NMDA receptor antagonist. J. Neurosci. 10, 909–925 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Bear, M. F. & Colman, H. Binocular competition in the control of geniculate cell size depends upon visual cortical N-methyl-D-aspartate receptor activation. Proc. Natl Acad. Sci. USA 87, 9246–9249 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Roberts, E. B., Meredith, M. A. & Ramoa, A. S. Suppression of NMDA receptor function using antisense DNA block ocular dominance plasticity while preserving visual responses. J. Neurophysiol. 80, 1021–1032 (1998).

    Article  CAS  PubMed  Google Scholar 

  78. Daw, N. W. et al. Injection of MK-801 affects ocular dominance shifts more than visual activity. J. Neurophysiol. 81, 204–215 (1999).

    Article  CAS  PubMed  Google Scholar 

  79. Liu, C. H., Heynen, A. J., Shuler, M. G. & Bear, M. F. Cannabinoid receptor blockade reveals parallel plasticity mechanisms in different layers of mouse visual cortex. Neuron 58, 340–345 (2008).

    Article  CAS  PubMed  Google Scholar 

  80. Yang, K. et al. The regulatory role of long-term depression in juvenile and adult mouse ocular dominance plasticity. Sci. Rep. 1, 203 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Bastrikova, N., Gardner, G. A., Reece, J. M., Jeromin, A. & Dudek, S. M. Synapse elimination accompanies functional plasticity in hippocampal neurons. Proc. Natl Acad. Sci. USA 105, 3123–3127 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Maffei, A., Nelson, S. B. & Turrigiano, G. G. Selective reconfiguration of layer 4 visual cortical circuitry by visual deprivation. Nature Neurosci. 7, 1353–1359 (2004).

    Article  CAS  PubMed  Google Scholar 

  83. Maffei, A., Nataraj, K., Nelson, S. B. & Turrigiano, G. G. Potentiation of cortical inhibition by visual deprivation. Nature 443, 81–84 (2006).

    Article  CAS  PubMed  Google Scholar 

  84. Smith, G. B., Heynen, A. J. & Bear, M. F. Bidirectional synaptic mechanisms of ocular dominance plasticity in visual cortex. Phil. Trans. R. Soc. B 364, 357–367 (2009).

    Article  PubMed  Google Scholar 

  85. Kirkwood, A. & Bear, M. F. Homosynaptic long-term depression in the visual cortex. J. Neurosci. 14, 3404–3412 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Carroll, R. C., Lissin, D. V., von Zastrow, M., Nicoll, R. A. & Malenka, R. C. Rapid redistribution of glutamate receptors contributes to long-term depression in hippocampal cultures. Nature Neurosci. 2, 454–460 (1999).

    Article  CAS  PubMed  Google Scholar 

  87. Lee, H. K., Kameyama, K., Huganir, R. L. & Bear, M. F. NMDA induces long-term synaptic depression and dephosphorylation of the GluR1 subunit of AMPA receptors in hippocampus. Neuron 21, 1151–1162 (1998).

    Article  CAS  PubMed  Google Scholar 

  88. Fitzjohn, S. M. et al. A characterisation of long-term depression induced by metabotropic glutamate receptor activation in the rat hippocampus in vitro. J. Physiol. 537, 421–430 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Huber, K. M., Roder, J. C. & Bear, M. F. Chemical induction of mGluR5- and protein synthesis-dependent long-term depression in hippocampal area CA1. J. Neurophysiol. 86, 321–325 (2001).

    Article  CAS  PubMed  Google Scholar 

  90. Griffiths, S. et al. Expression of long-term depression underlies visual recognition memory. Neuron 58, 186–194 (2008).

    Article  CAS  PubMed  Google Scholar 

  91. Kemp, A. & Manahan-Vaughan, D. Hippocampal long-term depression: master or minion in declarative memory processes? Trends Neurosci. 30, 111–118 (2007).

    Article  CAS  PubMed  Google Scholar 

  92. Allen, C. B., Celikel, T. & Feldman, D. E. Long-term depression induced by sensory deprivation during cortical map plasticity in vivo. Nature Neurosci. 6, 291–299 (2003).

    Article  CAS  PubMed  Google Scholar 

  93. Collingridge, G. L., Peineau, S., Howland, J. G. & Wang, Y. T. Long-term depression in the CNS. Nature Rev. Neurosci. 11, 459–473 (2010).

    Article  CAS  Google Scholar 

  94. Kirkwood, A., Rioult, M. C. & Bear, M. F. Experience-dependent modification of synaptic plasticity in visual cortex. Nature 381, 526–528 (1996).

    Article  CAS  PubMed  Google Scholar 

  95. Holland, L. L. & Wagner, J. J. Primed facilitation of homosynaptic long-term depression and depotentiation in rat hippocampus. J. Neurosci. 18, 887–894 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Abraham, W. C., Mason-Parker, S. E., Bear, M. F., Webb, S. & Tate, W. P. Heterosynaptic metaplasticity in the hippocampus in vivo: a BCM-like modifiable threshold for LTP. Proc. Natl Acad. Sci. USA 98, 10924–10929 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Hamada, M. et al. Bidirectional long-term motor cortical plasticity and metaplasticity induced by quadripulse transcranial magnetic stimulation. J. Physiol. 586, 3927–3947 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Benuskova, L., Diamond, M. E. & Ebner, F. F. Dynamic synaptic modification threshold: computational model of experience-dependent plasticity in adult rat barrel cortex. Proc. Natl Acad. Sci. USA 91, 4791–4795 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Xu, Z. et al. Metaplastic regulation of long-term potentiation/long-term depression threshold by activity-dependent changes of NR2A/NR2B ratio. J. Neurosci. 29, 8764–8773 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Bliem, B., Mueller-Dahlbaus, J. F. M., Dinse, H. R. & Ziemann, U. Homeostatic metaplasticity in human somatosensory cortex. J. Cogn. Neurosci. 20, 1517–1528 (2008).

    Article  PubMed  Google Scholar 

  101. Dunfield, D. & Haas, K. Metaplasticity governs natural experience-driven plasticity of nascent embryonic brain circuits. Neuron 64, 240–250 (2009).

    Article  CAS  PubMed  Google Scholar 

  102. Kind, P. C. et al. Correlated binocular activity guides recovery from monocular deprivation. Nature 416, 430–433 (2002).

    Article  CAS  PubMed  Google Scholar 

  103. Mitchell, D. E., Gingras, G. & Kind, P. C. Initial recovery of vision after early monocular deprivation in kittens is faster when both eyes are open. Proc. Natl Acad. Sci. USA 98, 11662–11667 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Philpot, B. D., Cho, K. K. & Bear, M. F. Obligatory role of NR2A for metaplasticity in visual cortex. Neuron 53, 495–502 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Iny, K., Heynen, A. J., Sklar, E. & Bear, M. F. Bidirectional modifications of visual acuity induced by monocular deprivation in juvenile and adult rats. J. Neurosci. 26, 7368–7374 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Abraham, W. C. & Bear, M. F. Metaplasticity: the plasticity of synaptic plasticity. Trends Neurosci. 19, 126–130 (1996).

    Article  CAS  PubMed  Google Scholar 

  107. Turrigiano, G. G. & Nelson, S. B. Homeostatic plasticity in the developing nervous system. Nature Rev. Neurosci. 5, 97–107 (2004).

    Article  CAS  Google Scholar 

  108. Sawtell, N. B. et al. NMDA receptor-dependent ocular dominance plasticity in adult visual cortex. Neuron 38, 977–985 (2003).

    Article  CAS  PubMed  Google Scholar 

  109. Sato, M. & Stryker, M. P. Distinctive features of adult ocular dominance plasticity. J. Neurosci. 28, 10278–10286 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Cho, K. K., Khibnik, L., Philpot, B. D. & Bear, M. F. The ratio of NR2A/B NMDA receptor subunits determines the qualities of ocular dominance plasticity in visual cortex. Proc. Natl Acad. Sci. USA 106, 5377–5382 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Kuo, M. C. & Dringenberg, H. C. Short-term (2 to 5 h) dark exposure lowers long-term potentiation (LTP) induction threshold in rat primary visual cortex. Brain Res. 1276, 58–66 (2009).

    Article  CAS  PubMed  Google Scholar 

  112. Feldman, D., Sherin, J. E., Press, W. A. & Bear, M. F. N-methyl-D-aspartate-evoked calcium uptake by kitten visual cortex maintained in vitro. Exp. Brain Res. 80, 252–259 (1990).

    Article  CAS  PubMed  Google Scholar 

  113. Gold, J. I. & Bear, M. F. A model of dendritic spine Ca2+ concentration exploring possible bases for a sliding synaptic modification threshold. Proc. Natl Acad. Sci. USA 91, 3941–3945 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Sobczyk, A. & Svoboda, K. Activity-dependent plasticity of the NMDA-receptor fractional Ca2+ current. Neuron 53, 17–24 (2007).

    Article  CAS  PubMed  Google Scholar 

  115. Kalantzis, G. & Shouval, H. Z. Structural plasticity can produce metaplasticity. PLoS ONE 4, e8062 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Philpot, B. D., Sekhar, A. K., Shouval, H. Z. & Bear, M. F. Visual experience and deprivation bidirectionally modify the composition and function of NMDA receptors in visual cortex. Neuron 29, 157–169 (2001).

    Article  CAS  PubMed  Google Scholar 

  117. Lee, M. C., Yasuda, R. & Ehlers, M. D. Metaplasticity at single glutamatergic synapses. Neuron 66, 859–870 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Cull-Candy, S. G. & Leszkiewicz, D. N. Role of distinct NMDA receptor subtypes at central synapses. Sci. STKE 2004, re16, (2004).

    PubMed  Google Scholar 

  119. Sobczyk, A., Scheuss, V. & Svoboda, K. NMDA receptor subunit-dependent [Ca2+] signaling in individual hippocampal dendritic spines. J. Neurosci. 25, 6037–6046 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Barria, A. & Malinow, R. NMDA receptor subunit composition controls synaptic plasticity by regulating binding to CaMKII. Neuron 48, 289–301 (2005).

    Article  CAS  PubMed  Google Scholar 

  121. Quinlan, E. M., Philpot, B. D., Huganir, R. L. & Bear, M. F. Rapid, experience-dependent expression of synaptic NMDA receptors in visual cortex in vivo. Nature Neurosci. 2, 352–357 (1999).

    Article  CAS  PubMed  Google Scholar 

  122. Quinlan, E. M., Olstein, D. H. & Bear, M. F. Bidirectional, experience-dependent regulation of N-methyl-D-aspartate receptor subunit composition in the rat visual cortex during postnatal development. Proc. Natl Acad. Sci. USA 96, 12876–12880 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Corson, J. et al. Sensory activity differentially modulates N-methyl-D-aspartate receptor subunits 2A and 2B in cortical layers. Neuroscience 163, 920–932 (2009).

    Article  CAS  PubMed  Google Scholar 

  124. Chen, W. S. & Bear, M. F. Activity-dependent regulation of NR2B translation contributes to metaplasticity in mouse visual cortex. Neuropharmacology 52, 200–214 (2007).

    Article  CAS  PubMed  Google Scholar 

  125. Cho, K. K. & Bear, M. F. Promoting neurological recovery of function via metaplasticity. Future Neurol. 5, 21–26 (2010).

    Google Scholar 

  126. Steele, P. M. & Mauk, M. D. Inhibitory control of LTP and LTD: stability of synapse strength. J. Neurophysiol. 81, 1559–1566 (1999).

    Article  CAS  PubMed  Google Scholar 

  127. Deisseroth, K., Bito, H., Schulman, H. & Tsien, R. W. Synaptic plasticity: a molecular mechanism for metaplasticity. Curr. Biol. 5, 1334–1338 (1995).

    Article  CAS  PubMed  Google Scholar 

  128. Zhang, L. et al. Hippocampal synaptic metaplasticity requires inhibitory autophosphorylation of Ca2+/calmodulin-dependent kinase II. J. Neurosci. 25, 7697–7707 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Hardingham, N., Wright, N., Dachtler, J. & Fox, K. Sensory deprivation unmasks a PKA-dependent synaptic plasticity mechanism that operates in parallel with CaMKII. Neuron 60, 861–874 (2008).

    Article  CAS  PubMed  Google Scholar 

  130. Narayanan, R. & Johnston, D. The h current is a candidate mechanism for regulating the sliding modification threshold in a BCM-like synaptic learning rule. J. Neurophysiol. 104, 1020–1033 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  131. Huh, G. S. et al. Functional requirement for class I MHC in CNS development and plasticity. Science 290, 2155–2159 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Huber, K. M., Sawtell, N. B. & Bear, M. F. Brain-derived neurotrophic factor alters the synaptic modification threshold in visual cortex. Neuropharmacology 37, 571–579 (1998).

    Article  CAS  PubMed  Google Scholar 

  133. Mayford, M., Wang, J., Kandel, E. R. & O'Dell, T. J. CaMKII regulates the frequency-response function of hippocampal synapses for the production of both LTD and LTP. Cell 81, 891–904 (1995).

    Article  CAS  PubMed  Google Scholar 

  134. Matta, J. A., Ashby, M. C., Sanz-Clemente, A., Roche, K. W. & Isaac, J. T. mGluR5 and NMDA receptors drive the experience- and activity-dependent NMDA receptor NR2B to NR2A subunit switch. Neuron 70, 339–351 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Philpot, B. D. & Zukin, R. S. Synapse-specific metaplasticity: to be silenced is not to silence 2B. Neuron 66, 814–816 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Bellone, C. & Nicoll, R. A. Rapid bidirectional switching of synaptic NMDA receptors. Neuron 55, 779–785 (2007).

    Article  CAS  PubMed  Google Scholar 

  137. Levy, W. B. & Steward, O. Synapses as associative memory elements in the hippocampal formation. Brain Res. 175, 233–245 (1979).

    Article  CAS  PubMed  Google Scholar 

  138. Wigstrom, H. & Gustafsson, B. Postsynaptic control of hippocampal long-term potentiation. J. Physiol. 81, 228–236 (1986).

    CAS  Google Scholar 

  139. Barrionuevo, G. & Brown, T. H. Associative long-term potentiation in hippocampal slices. Proc. Natl Acad. Sci. USA 80, 7347–7351 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Stewart, C. E., Moseley, M. J. & Fielder, A. R. Amblyopia therapy: an update. Strabismus 19, 91–98 (2011).

    Article  PubMed  Google Scholar 

  141. Hubel, D. H. & Wiesel, T. N. The period of susceptibility to the physiological effects of unilateral eye closure in kittens. J. Physiol. 206, 419–436 (1970).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Hofer, S. B., Mrsic-Flogel, T. D., Bonhoeffer, T. & Hubener, M. Lifelong learning: ocular dominance plasticity in mouse visual cortex. Curr. Opin. Neurobiol. 16, 451–459 (2006).

    Article  CAS  PubMed  Google Scholar 

  143. He, H. Y., Ray, B., Dennis, K. & Quinlan, E. M. Experience-dependent recovery of vision following chronic deprivation amblyopia. Nature Neurosci. 10, 1134–1136 (2007).

    Article  CAS  PubMed  Google Scholar 

  144. Montey, K. L. & Quinlan, E. M. Recovery from chronic monocular deprivation following reactivation of thalamocortical plasticity by dark exposure. Nature Commun. 2, 317 (2011).

    Article  Google Scholar 

  145. Shouval, H. Z. What is the appropriate description level for synaptic plasticity? Proc. Natl Acad. Sci. USA 108, 19103–19104 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Kerr, D. S. & Abraham, W. C. Cooperative interactions among afferents govern the induction of homosynaptic long-term depression in the hippocampus. Proc. Natl Acad. Sci. USA 92, 11637–11641 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Debanne, D., Gahwiler, B. H. & Thompson, S. M. Asynchronous pre- and postsynaptic activity induces associative long-term depression in area CA1 of the rat hippocampus in vitro. Proc. Natl Acad. Sci. USA 91, 1148–1152 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Markram, H., Lubke, J., Frotscher, M. & Sakmann, B. Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs. Science 275, 213–215 (1997).

    Article  CAS  PubMed  Google Scholar 

  149. Feldman, D. E. Timing-based LTP and LTD at vertical inputs to layer II/III pyramidal cells in rat barrel cortex. Neuron 27, 45–56 (2000).

    Article  CAS  PubMed  Google Scholar 

  150. Daw, N., Rao, Y., Wang, X. F., Fischer, Q. & Yang, Y. LTP and LTD vary with layer in rodent visual cortex. Vision Res. 44, 3377–3380 (2004).

    Article  PubMed  Google Scholar 

  151. Pfister, J. P. & Gerstner, W. Triplets of spikes in a model of spike timing-dependent plasticity. J. Neurosci. 26, 9673–9682 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Izhikevich, E. M. & Desai, N. S. Relating STDP to BCM. Neural Comput. 15, 1511–1523 (2003).

    Article  PubMed  Google Scholar 

  153. Gjorgjieva, J., Clopath, C., Audet, J. & Pfister, J. P. A triplet spike-timing-dependent plasticity model generalizes the Bienenstock–Cooper–Munro rule to higher-order spatiotemporal correlations. Proc. Natl Acad. Sci. USA 108, 19383–19388 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Abarbanel, H. D., Huerta, R. & Rabinovich, M. I. Dynamical model of long-term synaptic plasticity. Proc. Natl Acad. Sci. USA 99, 10132–10137 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Appleby, P. A. & Elliott, T. Synaptic and temporal ensemble interpretation of spike-timing-dependent plasticity. Neural Comput. 17, 2316–2336 (2005).

    Article  PubMed  Google Scholar 

  156. Karmarkar, U. R. & Buonomano, D. V. A model of spike-timing dependent plasticity: one or two coincidence detectors? J. Neurophysiol. 88, 507–513 (2002).

    Article  PubMed  Google Scholar 

  157. Castellani, G. C., Quinlan, E. M., Cooper, L. N. & Shouval, H. Z. A biophysical model of bidirectional synaptic plasticity: dependence on AMPA and NMDA receptors. Proc. Natl Acad. Sci. USA 98, 12772–12777 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Shouval, H. Z., Castellani, G. C., Blais, B. S., Yeung, L. C. & Cooper, L. N. Converging evidence for a simplified biophysical model of synaptic plasticity. Biol. Cybern. 87, 383–391 (2002).

    Article  PubMed  Google Scholar 

  159. Shouval, H. Z., Bear, M. F. & Cooper, L. N. A unified model of NMDA receptor-dependent bidirectional synaptic plasticity. Proc. Natl Acad. Sci. USA 99, 10831–10836 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Rachmuth, G., Shouval, H. Z., Bear, M. F. & Poon, C. S. A biophysically-based neuromorphic model of spike rate- and timing-dependent plasticity. Proc. Natl Acad. Sci. USA 108, e1266–e1274 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Malenka, R. C., Kauer, J. A., Zucker, R. S. & Nicoll, R. A. Postsynaptic calcium is sufficient for potentiation of hippocampal synaptic transmission. Science 242, 81–84 (1988).

    Article  CAS  PubMed  Google Scholar 

  162. Lynch, G., Larson, J., Kelso, S., Barrionuevo, G. & Schottler, F. Intracellular injections of EGTA block induction of hippocampal long-term potentiation. Nature 305, 719–721 (1983).

    Article  CAS  PubMed  Google Scholar 

  163. Artola, A., Brocher, S. & Singer, W. Different voltage-dependent thresholds for inducing long-term depression and long-term potentiation in slices of rat visual cortex. Nature 347, 69–72 (1990).

    Article  CAS  PubMed  Google Scholar 

  164. Cormier, R. J., Greenwood, A. C. & Connor, J. A. Bidirectional synaptic plasticity correlated with the magnitude of dendritic calcium transients above a threshold. J. Neurophysiol. 85, 399–406 (2001).

    Article  CAS  PubMed  Google Scholar 

  165. Ismailov, I., Kalikulov, D., Inoue, T. & Friedlander, M. J. The kinetic profile of intracellular calcium predicts long-term potentiation and long-term depression. J. Neurosci. 24, 9847–9861 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Stuart, G. J. & Sakmann, B. Active propagation of somatic action potentials into neocortical pyramidal cell dendrites. Nature 367, 69–72 (1994).

    Article  CAS  PubMed  Google Scholar 

  167. Magee, J. C. & Johnston, D. A synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons. Science 275, 209–213 (1997).

    Article  CAS  PubMed  Google Scholar 

  168. Bliss, T. V., Burns, B. D. & Uttley, A. M. Factors affecting the conductivity of pathways in the cerebral cortex. J. Physiol. 195, 339–367 (1968).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Bindman, L. J., Murphy, K. P. & Pockett, S. Postsynaptic control of the induction of long-term changes in efficacy of transmission at neocortical synapses in slices of rat brain. J. Neurophysiol. 60, 1053–1065 (1988).

    Article  CAS  PubMed  Google Scholar 

  170. Bramham, C. R. & Srebro, B. Induction of long-term depression and potentiation by low- and high-frequency stimulation in the dentate area of the anesthetized rat: magnitude, time course and EEG. Brain Res. 405, 100–107 (1987).

    Article  CAS  PubMed  Google Scholar 

  171. Hirsch, J. C. & Crepel, F. Use-dependent changes in synaptic efficacy in rat prefrontal neurons in vitro. J. Physiol. 427, 31–49 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Barrionuevo, G., Schottler, F. & Lynch, G. The effects of low frequency stimulation on control and “potentiated” synaptic responses in the hippocampus. Life Sci. 27, 2385–2391 (1980).

    Article  CAS  PubMed  Google Scholar 

  173. Staubli, U. & Lynch, G. Stable depression of potentiated synaptic responses in the hippocampus with 1–5 Hz stimulation. Brain Res. 513, 113–118 (1990).

    Article  CAS  PubMed  Google Scholar 

  174. Fujii, S., Saito, K., Miyakawa, H., Ito, K. & Kato, H. Reversal of long-term potentiation (depotentiation) induced by tetanus stimulation of the input to CA1 neurons of guinea pig hippocampal slices. Brain Res. 555, 112–122 (1991).

    Article  CAS  PubMed  Google Scholar 

  175. Arai, A., Larson, J. & Lynch, G. Anoxia reveals a vulnerable period in the development of long-term potentiation. Brain Res. 511, 353–357 (1990).

    Article  CAS  PubMed  Google Scholar 

  176. Lynch, G. S., Dunwiddie, T. & Gribkoff, V. Heterosynaptic depression: a postsynaptic correlate of long-term potentiation. Nature 266, 737–739 (1977).

    Article  CAS  PubMed  Google Scholar 

  177. Abraham, W. C. & Goddard, G. V. Asymmetric relationships between homosynaptic long-term potentiation and heterosynaptic long-term depression. Nature 305, 717–719 (1983).

    Article  CAS  PubMed  Google Scholar 

  178. Tsumoto, T. & Suda, K. Cross-depression: an electrophysiological manifestation of binocular competition in the developing visual cortex. Brain Res. 168, 190–194 (1979).

    Article  CAS  PubMed  Google Scholar 

  179. Dunwiddie, T. & Lynch, G. Long-term potentiation and depression of synaptic responses in the rat hippocampus: localization and frequency dependency. J. Physiol. 276, 353–367 (1978).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Wickens, J. R. & Abraham, W. C. The involvement of L-type calcium channels in heterosynaptic long-term depression in the hippocampus. Neurosci. Lett. 130, 128–132 (1991).

    Article  CAS  PubMed  Google Scholar 

  181. Bear, M. F. & Abraham, W. C. Long-term depression in hippocampus. Annu. Rev. Neurosci. 19, 437–462 (1996).

    Article  CAS  PubMed  Google Scholar 

  182. Ito, M. & Kano, M. Long-lasting depression of parallel fiber-Purkinje cell transmission induced by conjunctive stimulation of parallel fibers and climbing fibers in the cerebellar cortex. Neurosci. Lett. 33, 253–258 (1982).

    Article  CAS  PubMed  Google Scholar 

  183. Linden, D. J. & Connor, J. A. Long-term synaptic depression. Annu. Rev. Neurosci. 18, 319–357 (1995).

    Article  CAS  PubMed  Google Scholar 

  184. Stanton, P. K. & Sejnowski, T. J. Associative long-term depression in the hippocampus induced by hebbian covariance. Nature 339, 215–218 (1989).

    Article  CAS  PubMed  Google Scholar 

  185. Goldman, R. S., Chavez-Noriega, L. E. & Stevens, C. F. Failure to reverse long-term potentiation by coupling sustained presynaptic activity and N-methyl-D-aspartate receptor blockade. Proc. Natl Acad. Sci. USA 87, 7165–7169 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Mulkey, R. M., Herron, C. E. & Malenka, R. C. An essential role for protein phosphatases in hippocampal long-term depression. Science 261, 1051–1055 (1993).

    Article  CAS  PubMed  Google Scholar 

  187. Cooper, L. N., Intrator, N., Blais, B. & Shouval, H. Theory of Cortical Plasticity (World Scientific Publishing, 2004).

    Book  Google Scholar 

  188. Stryker, M. P. & Harris, W. A. Binocular impulse blockade prevents the formation of ocular dominance columns in cat visual cortex. J. Neurosci. 6, 2117–2133 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Steriade, M., McCormick, D. A. & Sejnowski, T. J. Thalamocortical oscillations in the sleeping and aroused brain. Science 262, 679–685 (1993).

    Article  CAS  PubMed  Google Scholar 

  190. McCurry, C. L. et al. Loss of Arc renders the visual cortex impervious to the effects of sensory experience or deprivation. Nature Neurosci. 13, 450–457 (2010).

    Article  CAS  PubMed  Google Scholar 

  191. Dolen, G. et al. Correction of fragile X syndrome in mice. Neuron 56, 955–962 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank the many colleagues, both theoretical and experimental, with whom they have worked these many years. Our collaborative research has been supported by the US Office of Naval Research, the Army Research Office, the Air Force Office of Scientific Research, the National Science Foundation, the US National Institutes of Health, the Howard Hughes Medical Institute, the Dana Foundation and the Ittleson Family Foundation.

Author information

Authors and Affiliations

  1. Department of Physics, Leon N Cooper is at the Institute for Brain and Neural Systems, Brown University, Providence, Rhode Island 02912, USA.,

    Leon N Cooper

  2. Department of Brain and Cognitive Sciences, Mark F. Bear is at the Howard Hughes Medical Institute, and at the Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.,

    Mark F. Bear

Authors
  1. Leon N Cooper
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark F. Bear
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Leon N Cooper or Mark F. Bear.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Mark Bear's homepage

The Institute for Brain and Neural Systems, Brown University

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Cooper, L., Bear, M. The BCM theory of synapse modification at 30: interaction of theory with experiment. Nat Rev Neurosci 13, 798–810 (2012). https://doi.org/10.1038/nrn3353

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn3353

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing