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Cortical rewiring and information storage

Abstract

Current thinking about long-term memory in the cortex is focused on changes in the strengths of connections between neurons. But ongoing structural plasticity in the adult brain, including synapse formation/elimination and remodelling of axons and dendrites, suggests that memory could also depend on learning-induced changes in the cortical ‘wiring diagram’. Given that the cortex is sparsely connected, wiring plasticity could provide a substantial boost in storage capacity, although at a cost of more elaborate biological machinery and slower learning.

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Figure 1: Structural circuit plasticity and the wiring diagram.
Figure 2: Structural plasticity.
Figure 3: Actual and potential connectivity from a presynaptic population onto a postsynaptic unit.

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References

  1. McGaugh, J. L. Memory — a century of consolidation. Science 287, 248–251 (2000).

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Kandel, E. R. & Squire, L. R. Memory: From Mind to Molecules (Scientific American, New York, 1999).

    Google Scholar 

  3. Hebb, D. O. The Organization of Behavior (Wiley, New York, 1949).

    Google Scholar 

  4. McClelland, J. L. & Rumelhart, D. E. Distributed memory and the representation of general and specific information. J. Exp. Psychol. Gen. 114, 159–197 (1985).

    CAS  PubMed  Google Scholar 

  5. MacKay, D. Information Theory, Inference and Learning Algorithms (Cambridge Univ. Press, Cambridge, UK, 2003).

    MATH  Google Scholar 

  6. Bishop, C. Neural Networks for Pattern Recognition (Oxford Univ. Press, Oxford, 1995).

    MATH  Google Scholar 

  7. Kullmann, D. M. & Siegelbaum, S. A. The site of expression of NMDA receptor-dependent LTP: new fuel for an old fire. Neuron 15, 997–1002 (1995).

    CAS  PubMed  Google Scholar 

  8. Turner, A. M. & Greenough, W. T. Differential rearing effects on rat visual cortex synapses. I. Synaptic and neuronal density and synapses per neuron. Brain Res. 329, 195–203 (1985).

    CAS  PubMed  Google Scholar 

  9. Knott, G. W., Quairiaux, C., Genoud, C. & Welker, E. Formation of dendritic spines with GABAergic synapses induced by whisker stimulation in adult mice. Neuron 34, 265–273 (2002).

    CAS  PubMed  Google Scholar 

  10. Trachtenberg, J. T. et al. Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420, 788–794 (2002).

    ADS  CAS  PubMed  Google Scholar 

  11. Volkmar, F. R. & Greenough, W. T. Differential rearing effects on rat visual cortical plasticity. Science 176, 1445–1447 (1972).

    ADS  CAS  PubMed  Google Scholar 

  12. Chang, F. L. & Greenough, W. T. Lateralized effects of monocular training on dendritic branching in adult split-brain rats. Brain Res. 232, 283–292 (1982).

    CAS  PubMed  Google Scholar 

  13. Darian-Smith, C. & Gilbert, C. D. Axonal sprouting accompanies functional reorganization in adult cat striate cortex. Nature 368, 737–740 (1994).

    ADS  CAS  PubMed  Google Scholar 

  14. Florence, S. L., Taub, H. B. & Kaas, J. H. Large-scale sprouting of cortical connections after peripheral injury in adult macaque monkeys. Science 282, 1117–1121 (1998).

    ADS  CAS  PubMed  Google Scholar 

  15. Bailey, C. H. & Kandel, E. R. Structural changes accompanying memory formation. Annu. Rev. Physiol. 55, 397–426 (1993).

    CAS  PubMed  Google Scholar 

  16. Lisman, J. & Morris, R. G. Memory. Why is the cortex a slow learner? Nature 411, 248–249 (2001).

    ADS  CAS  PubMed  Google Scholar 

  17. Frankland, P. W., O'Brien, C., Ohno, M., Kirkwood, A. & Silva, A. J. Alpha-CaMKII-dependent plasticity in the cortex is required for permanent memory. Nature 411, 309–313 (2001).

    ADS  CAS  PubMed  Google Scholar 

  18. Grutzendler, J., Kasthuri, N. & Gan, W. B. Long-term dendritic spine stability in the adult cortex. Nature 420, 812–816 (2002).

    ADS  CAS  PubMed  Google Scholar 

  19. Mizrahi, A. & Katz, L. C. Dendritic stability in the adult olfactory bulb. Nature Neurosci. 6, 1201–1207 (2003).

    CAS  PubMed  Google Scholar 

  20. Levy, W. B. & Desmond, N. L. in Synaptic Modification, Neuron Selectivity and Nervous System Organization (eds Levy, W. B., Anderson, J. C. & Lehmkuhle, S.) 105–121 (Lawrence Erlbaum, Hillsdale, New Jersey, 1985).

    Google Scholar 

  21. Mel, B. W. in Advances in Neural Information Processing Systems (eds Moody, J., Hanson, S. & Lippmann, R.) 35–42 (Morgan Kaufmann, San Mateo, California, 1992).

    Google Scholar 

  22. Poirazi, P. & Mel, B. W. Impact of active dendrites and structural plasticity on the memory capacity of neural tissue. Neuron 29, 779–796 (2001).

    CAS  PubMed  Google Scholar 

  23. Stepanyants, A., Hof, P. R. & Chklovskii, D. B. Geometry and structural plasticity of synaptic connectivity. Neuron 34, 275–288 (2002).

    CAS  PubMed  MATH  Google Scholar 

  24. Mel, B. W. Have we been hebbing down the wrong path? Neuron 34, 175–177 (2002).

    CAS  PubMed  Google Scholar 

  25. Braitenberg, V. & Schutz, A. Anatomy of the Cortex (Springer, Berlin, 1991).

    Google Scholar 

  26. Holmgren, C., Harkany, T., Svennenfors, B. & Zilberter, Y. Pyramidal cell communication within local networks in layer 2/3 of rat neocortex. J. Physiol. 551, 139–153 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Hubel, D. H. & Wiesel, T. N. Receptive fields, binocular interaction and functional architecture in the cat's visual cortex. J. Physiol. (Lond.) 148, 574–591 (1962).

    Google Scholar 

  28. Mountcastle, V. B. Modality and topographic properties of single neurons of cat's somatic sensory cortex. J. Neurophysiol. 20, 408–434 (1957).

    CAS  PubMed  Google Scholar 

  29. Rall, W. & Segev, I. in Synaptic Function (eds Edelman, G. M., Gall, W. E. & Cowan, W. M.) 603–636 (Wiley, New York, 1987).

    Google Scholar 

  30. Koch, C., Poggio, T. & Torre, V. Retinal ganglion cells: a functional interpretation of dendritic morphology. Phil. Trans. R. Soc. Lond. B 298, 227–263 (1982).

    ADS  CAS  Google Scholar 

  31. Shepherd, G. M. & Brayton, R. K. Logic operations are properties of computer-simulated interactions between excitable dendritic spines. Neuroscience 21, 151–165 (1987).

    CAS  PubMed  Google Scholar 

  32. Mel, B. W. Synaptic integration in an excitable dendritic tree. J. Neurophysiol. 70, 1086–1101 (1993).

    CAS  PubMed  Google Scholar 

  33. Poirazi, P., Brannon, T. & Mel, B. W. Arithmetic of subthreshold synaptic summation in a model CA1 pyramidal cell. Neuron 37, 977–987 (2003).

    CAS  PubMed  Google Scholar 

  34. Polsky, A., Mel, B. W. & Schiller, J. Computational subunits in thin dendrites of pyramidal cells. Nature Neurosci. 7, 621–627 (2004).

    CAS  PubMed  Google Scholar 

  35. Svoboda, K., Denk, W., Kleinfeld, D. & Tank, D. W. In vivo dendritic calcium dynamics in neocortical pyramidal neurons. Nature 385, 161–165 (1997).

    ADS  CAS  PubMed  Google Scholar 

  36. Stepanyants, A., Tamas, G. & Chklovskii, D. B. Class-specific features of neuronal wiring. Neuron 43, 251–259 (2004).

    CAS  PubMed  Google Scholar 

  37. Hellwig, B. A quantitative analysis of the local connectivity between pyramidal neurons in layers 2/3 of the rat visual cortex. Biol. Cybern. 82, 111–121 (2000).

    CAS  PubMed  Google Scholar 

  38. Kalisman, N., Silberberg, G. & Markram, H. Deriving physical connectivity from neuronal morphology. Biol. Cybern. 88, 210–208 (2003).

    PubMed  MATH  Google Scholar 

  39. Stepanyants, A. B., Hirsh, J. A., Martinez, L. M. & Chklovskii, D. B. Domains of “potential” connectivity of cortical spiny neurons. Abstract. Society for Neuroscience Annual Meeting, New Orleans (2003).

  40. Markram, H., Lubke, J., Frotscher, M., Roth, A. & Sakmann, B. Physiology and anatomy of synaptic connections between thick tufted pyramidal neurones in the developing rat neocortex. J. Physiol. 500, 409–440 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Oheim, M., Beaurepaire, E., Chaigneau, E., Mertz, J. & Charpak, S. Two-photon microscopy in brain tissue: parameters influencing the imaging depth. J. Neurosci. Methods 111, 29–37 (2001).

    CAS  PubMed  Google Scholar 

  42. Levene, M. J., Dombeck, D. A., Kasischke, K. A., Molloy, R. P. & Webb, W. W. In vivo multiphoton microscopy of deep brain tissue. J. Neurophysiol. 91, 1908–1912 (2004).

    PubMed  Google Scholar 

  43. Oertner, T. G., Sabatini, B. S., Nimchinsky, E. A. & Svoboda, K. Facilitation at single synapses probed with optical quantal analysis. Nature Neurosci. 5, 657–664 (2002).

    CAS  PubMed  Google Scholar 

  44. Chklovskii, D. B. Synaptic connectivity and neuronal morphology; two sides of the same coin. Neuron 43, 609–617 (2004).

    CAS  PubMed  Google Scholar 

  45. Kolb, B. & Whishaw, I. Q. Brain plasticity and behaviour. Annu. Rev. Psychol. 49, 43–64 (1998).

    CAS  PubMed  Google Scholar 

  46. Faherty, C. J., Kerley, D. & Smeyne, R. J. A Golgi–Cox morphological analysis of neuronal changes induced by environmental enrichment. Brain Res. Dev. Brain Res. 141, 55–61 (2003).

    CAS  PubMed  Google Scholar 

  47. Greenough, W. T., Volkmar, F. R. & Juraska, J. M. Effects of rearing complexity on dendritic branching in frontolateral and temporal cortex of the rat. Exp. Neurol. 41, 371–378 (1973).

    CAS  PubMed  Google Scholar 

  48. Merzenich, M. M. et al. Somatosensory cortical map changes following digit amputation in adult monkeys. J. Comp. Neurol. 224, 591–605 (1984).

    CAS  PubMed  Google Scholar 

  49. Pons, T. P. et al. Massive cortical reorganization after sensory deafferentiation in adult macaques. Science 252, 1857–1860 (1991).

    ADS  CAS  PubMed  Google Scholar 

  50. Flor, H. et al. Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature 375, 482–484 (1995).

    ADS  CAS  PubMed  Google Scholar 

  51. Heinen, S. J. & Skavenski, A. A. Recovery of visual responses in foveal V1 neurons following bilateral foveal lesions in adult monkey. Exp. Brain Res. 83, 670–674 (1991).

    CAS  PubMed  Google Scholar 

  52. Gilbert, C. D. Adult cortical dynamics. Physiol. Rev. 78, 467–485 (1998).

    ADS  CAS  PubMed  Google Scholar 

  53. Jones, E. G. & Pons, T. P. Thalamic and brainstem contributions to large-scale plasticity of primate somatosensory cortex. Science 282, 1121–1125 (1998).

    ADS  CAS  PubMed  Google Scholar 

  54. Chklovskii, D. B. & Koulakov, A. A. Maps in the brain: what can we learn from them? Annu. Rev. Neurosci. 27, 369–392 (2004).

    CAS  PubMed  Google Scholar 

  55. Jontes, J. D. & Smith, S. J. Filopodia, spines, and the generation of synaptic diversity. Neuron 27, 11–14 (2000).

    CAS  PubMed  Google Scholar 

  56. Cline, H. T. Activity-dependent plasticity in the visual systems of frogs and fish. Trends Neurosci. 14, 104–111 (1991).

    CAS  PubMed  Google Scholar 

  57. Liao, D., Hessler, N. A. & Malinow, R. Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice. Nature 375, 400–404 (1995).

    ADS  CAS  PubMed  Google Scholar 

  58. Isaac, J. T., Nicoll, R. A. & Malenka, R. C. Evidence for silent synapses: implications for the expression of LTP. Neuron 15, 427–434 (1995).

    CAS  PubMed  Google Scholar 

  59. Baude, A. et al. The metabotropic glutamate receptor (mGluR1 alpha) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction. Neuron 11, 771–787 (1993).

    CAS  PubMed  Google Scholar 

  60. Tessier-Lavigne, M. & Goodman, C. S. The molecular biology of axon guidance. Science 274, 1123–1133 (1996).

    ADS  CAS  PubMed  Google Scholar 

  61. McCaig, C. D., Rajnicek, A. M., Song, B. & Zhao, M. Has electrical growth cone guidance found its potential? Trends Neurosci. 25, 354–359 (2002).

    CAS  PubMed  Google Scholar 

  62. Lisman, J., Lichtman, J. W. & Sanes, J. R. LTP: perils and progress. Nature Rev. Neurosci. 4, 926–929 (2003).

    CAS  Google Scholar 

  63. Buonomano, D. V. & Merzenich, M. M. Cortical plasticity: from synapses to maps. Annu. Rev. Neurosci. 21, 149–186 (1998).

    CAS  PubMed  Google Scholar 

  64. Martin, S. J., Grimwood, P. D. & Morris, R. G. Synaptic plasticity and memory: an evaluation of the hypothesis. Annu. Rev. Neurosci. 23, 649–711 (2000).

    CAS  PubMed  Google Scholar 

  65. Rioult-Pedotti, M. S., Friedman, D. & Donoghue, J. P. Learning-induced LTP in neocortex. Science 290, 533–536 (2000).

    ADS  CAS  PubMed  Google Scholar 

  66. Finnerty, G. T., Roberts, L. S. & Connors, B. W. Sensory experience modifies the short-term dynamics of neocortical synapses. Nature 400, 367–371 (1999).

    ADS  CAS  PubMed  Google Scholar 

  67. Takahashi, T., Svoboda, K. & Malinow, R. Experience strengthening transmission by driving AMPA receptors into synapses. Science 299, 1585–1588 (2003).

    ADS  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  69. Antonini, A. & Stryker, M. P. Rapid remodeling of axonal arbors in the visual cortex. Science 260, 1819–1821 (1993).

    ADS  CAS  PubMed  Google Scholar 

  70. Maravall, M., Koh, I. Y., Lindquist, W. B. & Svoboda, K. Experience-dependent changes in basal dendritic branching of layer 2/3 pyramidal neurons during a critical period for developmental plasticity in rat barrel cortex. Cereb. Cortex 14, 655–664 (2004).

    PubMed  Google Scholar 

  71. Lendvai, B., Stern, E., Chen, B. & Svoboda, K. Experience-dependent plasticity of dendritic spines in the developing rat barrel cortex in vivo. Nature 404, 876–881 (2000).

    ADS  CAS  PubMed  Google Scholar 

  72. Nimchinsky, E. A., Yasuda, R., Oertner, T. G. & Svoboda, K. The number of glutamate receptors opened by synaptic stimulation in single hippocampal spines. J. Neurosci. 24, 2054–2064 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Sabatini, B. L. & Svoboda, K. Analysis of calcium channels in single spines using optical fluctuation analysis. Nature 408, 589–593 (2000).

    ADS  CAS  PubMed  Google Scholar 

  74. Ehlers, M. D. Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system. Nature Neurosci. 6, 231–242 (2003).

    CAS  PubMed  Google Scholar 

  75. Shi, S. H. et al. Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science 284, 1811–1816 (1999).

    CAS  PubMed  Google Scholar 

  76. Maletic-Savatic, M., Malinow, R. & Svoboda, K. Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. Science 283, 1923–1927 (1999).

    ADS  CAS  PubMed  Google Scholar 

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

    ADS  CAS  PubMed  Google Scholar 

  78. Toni, N., Buchs, P. A., Nikonenko, I., Bron, C. R. & Muller, D. LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite. Nature 402, 421–425 (1999).

    ADS  CAS  PubMed  Google Scholar 

  79. Ziv, N. E. & Garner, C. C. Principles of glutamatergic synapse formation: seeing the forest for the trees. Curr. Opin. Neurobiol. 11, 536–543 (2001).

    CAS  PubMed  Google Scholar 

  80. Wu, G., Malinow, R. & Cline, H. T. Maturation of a central glutamatergic synapse. Science 274, 972–976 (1996).

    ADS  CAS  PubMed  Google Scholar 

  81. Xiao, M. Y., Wasling, P., Hanse, E. & Gustafsson, B. Creation of AMPA-silent synapses in the neonatal hippocampus. Nature Neurosci. 7, 236–243 (2004).

    CAS  PubMed  Google Scholar 

  82. Crair, M. C. & Malenka, R. C. A critical period for long-term potentiation at thalamocortical synapses. Nature 375, 325–328 (1995).

    ADS  CAS  PubMed  Google Scholar 

  83. Wu, G. Y. & Cline, H. T. Stabilization of dendritic arbor structure in vivo by CaMKII. Science 279, 222–226 (1998).

    ADS  CAS  PubMed  Google Scholar 

  84. Jourdain, P., Fukunaga, K. & Muller, D. Calcium/calmodulin-dependent protein kinase II contributes to activity-dependent filopodia growth and spine formation. J. Neurosci. 23, 10645–10649 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Pratt, K. G., Watt, A. J., Griffith, L. C., Nelson, S. B. & Turrigiano, G. G. Activity-dependent remodeling of presynaptic inputs by postsynaptic expression of activated CaMKII. Neuron 39, 269–281 (2003).

    CAS  PubMed  Google Scholar 

  86. McClelland, J. L., McNaughton, B. L. & O'Reilly, R. C. Why there are complementary learning systems in the hippocampus and neocortex: insights from the successes and failures of connectionist models of learning and memory. Psychol. Rev. 102, 419–457 (1995).

    PubMed  Google Scholar 

  87. Cui, Z. et al. Inducible and reversible NR1 knockout reveals crucial role of the NMDA receptor in preserving remote memories in the brain. Neuron 41, 781–793 (2004).

    CAS  PubMed  Google Scholar 

  88. Frankland, P. W., Bontempi, B., Talton, L. E., Kaczmarek, L. & Silva, A. J. The involvement of the anterior cingulate cortex in remote contextual fear memory. Science 304, 881–883 (2004).

    ADS  CAS  PubMed  Google Scholar 

  89. Petersen, C. C., Malenka, R. C., Nicoll, R. A. & Hopfield, J. J. All-or-none potentiation at CA3–CA1 synapses. Proc. Natl Acad. Sci. USA 95, 4732–4737 (1998).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  90. Poirazi, P. & Mel, B.W. Choice and value flexibility jointly contribute to the capacity of a subsampled quadratic classifier. Neural Comput. 12, 1189–1205 (2000).

    CAS  PubMed  Google Scholar 

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Chklovskii, D., Mel, B. & Svoboda, K. Cortical rewiring and information storage. Nature 431, 782–788 (2004). https://doi.org/10.1038/nature03012

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