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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McGaugh, J. L. Memory — a century of consolidation. Science 287, 248–251 (2000).
Kandel, E. R. & Squire, L. R. Memory: From Mind to Molecules (Scientific American, New York, 1999).
Hebb, D. O. The Organization of Behavior (Wiley, New York, 1949).
McClelland, J. L. & Rumelhart, D. E. Distributed memory and the representation of general and specific information. J. Exp. Psychol. Gen. 114, 159–197 (1985).
MacKay, D. Information Theory, Inference and Learning Algorithms (Cambridge Univ. Press, Cambridge, UK, 2003).
Bishop, C. Neural Networks for Pattern Recognition (Oxford Univ. Press, Oxford, 1995).
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).
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).
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).
Trachtenberg, J. T. et al. Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420, 788–794 (2002).
Volkmar, F. R. & Greenough, W. T. Differential rearing effects on rat visual cortical plasticity. Science 176, 1445–1447 (1972).
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).
Darian-Smith, C. & Gilbert, C. D. Axonal sprouting accompanies functional reorganization in adult cat striate cortex. Nature 368, 737–740 (1994).
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).
Bailey, C. H. & Kandel, E. R. Structural changes accompanying memory formation. Annu. Rev. Physiol. 55, 397–426 (1993).
Lisman, J. & Morris, R. G. Memory. Why is the cortex a slow learner? Nature 411, 248–249 (2001).
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).
Grutzendler, J., Kasthuri, N. & Gan, W. B. Long-term dendritic spine stability in the adult cortex. Nature 420, 812–816 (2002).
Mizrahi, A. & Katz, L. C. Dendritic stability in the adult olfactory bulb. Nature Neurosci. 6, 1201–1207 (2003).
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).
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).
Poirazi, P. & Mel, B. W. Impact of active dendrites and structural plasticity on the memory capacity of neural tissue. Neuron 29, 779–796 (2001).
Stepanyants, A., Hof, P. R. & Chklovskii, D. B. Geometry and structural plasticity of synaptic connectivity. Neuron 34, 275–288 (2002).
Mel, B. W. Have we been hebbing down the wrong path? Neuron 34, 175–177 (2002).
Braitenberg, V. & Schutz, A. Anatomy of the Cortex (Springer, Berlin, 1991).
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).
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).
Mountcastle, V. B. Modality and topographic properties of single neurons of cat's somatic sensory cortex. J. Neurophysiol. 20, 408–434 (1957).
Rall, W. & Segev, I. in Synaptic Function (eds Edelman, G. M., Gall, W. E. & Cowan, W. M.) 603–636 (Wiley, New York, 1987).
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).
Shepherd, G. M. & Brayton, R. K. Logic operations are properties of computer-simulated interactions between excitable dendritic spines. Neuroscience 21, 151–165 (1987).
Mel, B. W. Synaptic integration in an excitable dendritic tree. J. Neurophysiol. 70, 1086–1101 (1993).
Poirazi, P., Brannon, T. & Mel, B. W. Arithmetic of subthreshold synaptic summation in a model CA1 pyramidal cell. Neuron 37, 977–987 (2003).
Polsky, A., Mel, B. W. & Schiller, J. Computational subunits in thin dendrites of pyramidal cells. Nature Neurosci. 7, 621–627 (2004).
Svoboda, K., Denk, W., Kleinfeld, D. & Tank, D. W. In vivo dendritic calcium dynamics in neocortical pyramidal neurons. Nature 385, 161–165 (1997).
Stepanyants, A., Tamas, G. & Chklovskii, D. B. Class-specific features of neuronal wiring. Neuron 43, 251–259 (2004).
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).
Kalisman, N., Silberberg, G. & Markram, H. Deriving physical connectivity from neuronal morphology. Biol. Cybern. 88, 210–208 (2003).
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).
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).
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).
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).
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).
Chklovskii, D. B. Synaptic connectivity and neuronal morphology; two sides of the same coin. Neuron 43, 609–617 (2004).
Kolb, B. & Whishaw, I. Q. Brain plasticity and behaviour. Annu. Rev. Psychol. 49, 43–64 (1998).
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).
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).
Merzenich, M. M. et al. Somatosensory cortical map changes following digit amputation in adult monkeys. J. Comp. Neurol. 224, 591–605 (1984).
Pons, T. P. et al. Massive cortical reorganization after sensory deafferentiation in adult macaques. Science 252, 1857–1860 (1991).
Flor, H. et al. Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature 375, 482–484 (1995).
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).
Gilbert, C. D. Adult cortical dynamics. Physiol. Rev. 78, 467–485 (1998).
Jones, E. G. & Pons, T. P. Thalamic and brainstem contributions to large-scale plasticity of primate somatosensory cortex. Science 282, 1121–1125 (1998).
Chklovskii, D. B. & Koulakov, A. A. Maps in the brain: what can we learn from them? Annu. Rev. Neurosci. 27, 369–392 (2004).
Jontes, J. D. & Smith, S. J. Filopodia, spines, and the generation of synaptic diversity. Neuron 27, 11–14 (2000).
Cline, H. T. Activity-dependent plasticity in the visual systems of frogs and fish. Trends Neurosci. 14, 104–111 (1991).
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).
Isaac, J. T., Nicoll, R. A. & Malenka, R. C. Evidence for silent synapses: implications for the expression of LTP. Neuron 15, 427–434 (1995).
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).
Tessier-Lavigne, M. & Goodman, C. S. The molecular biology of axon guidance. Science 274, 1123–1133 (1996).
McCaig, C. D., Rajnicek, A. M., Song, B. & Zhao, M. Has electrical growth cone guidance found its potential? Trends Neurosci. 25, 354–359 (2002).
Lisman, J., Lichtman, J. W. & Sanes, J. R. LTP: perils and progress. Nature Rev. Neurosci. 4, 926–929 (2003).
Buonomano, D. V. & Merzenich, M. M. Cortical plasticity: from synapses to maps. Annu. Rev. Neurosci. 21, 149–186 (1998).
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).
Rioult-Pedotti, M. S., Friedman, D. & Donoghue, J. P. Learning-induced LTP in neocortex. Science 290, 533–536 (2000).
Finnerty, G. T., Roberts, L. S. & Connors, B. W. Sensory experience modifies the short-term dynamics of neocortical synapses. Nature 400, 367–371 (1999).
Takahashi, T., Svoboda, K. & Malinow, R. Experience strengthening transmission by driving AMPA receptors into synapses. Science 299, 1585–1588 (2003).
Heynen, A. J. et al. Molecular mechanism for loss of visual cortical responsiveness following brief monocular deprivation. Nature Neurosci. 6, 854–862 (2003).
Antonini, A. & Stryker, M. P. Rapid remodeling of axonal arbors in the visual cortex. Science 260, 1819–1821 (1993).
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).
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).
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).
Sabatini, B. L. & Svoboda, K. Analysis of calcium channels in single spines using optical fluctuation analysis. Nature 408, 589–593 (2000).
Ehlers, M. D. Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system. Nature Neurosci. 6, 231–242 (2003).
Shi, S. H. et al. Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science 284, 1811–1816 (1999).
Maletic-Savatic, M., Malinow, R. & Svoboda, K. Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. Science 283, 1923–1927 (1999).
Engert, F. & Bonhoeffer, T. Dendritic spine changes associated with hippocampal long-term synaptic plasticity. Nature 399, 66–70 (1999).
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).
Ziv, N. E. & Garner, C. C. Principles of glutamatergic synapse formation: seeing the forest for the trees. Curr. Opin. Neurobiol. 11, 536–543 (2001).
Wu, G., Malinow, R. & Cline, H. T. Maturation of a central glutamatergic synapse. Science 274, 972–976 (1996).
Xiao, M. Y., Wasling, P., Hanse, E. & Gustafsson, B. Creation of AMPA-silent synapses in the neonatal hippocampus. Nature Neurosci. 7, 236–243 (2004).
Crair, M. C. & Malenka, R. C. A critical period for long-term potentiation at thalamocortical synapses. Nature 375, 325–328 (1995).
Wu, G. Y. & Cline, H. T. Stabilization of dendritic arbor structure in vivo by CaMKII. Science 279, 222–226 (1998).
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).
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).
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).
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).
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).
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).
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).
The authors declare no competing financial interests.
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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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