Massive restructuring of neuronal circuits during functional reorganization of adult visual cortex

Article metrics


The cerebral cortex has the ability to adapt to altered sensory inputs. In the visual cortex, a small lesion to the retina causes the deprived cortical region to become responsive to adjacent parts of the visual field. This extensive topographic remapping is assumed to be mediated by the rewiring of intracortical connections, but the dynamics of this reorganization process remain unknown. We used repeated intrinsic signal and two-photon imaging to monitor functional and structural alterations in adult mouse visual cortex over a period of months following a retinal lesion. The rate at which dendritic spines were lost and gained increased threefold after a small retinal lesion, leading to an almost complete replacement of spines in the deafferented cortex within 2 months. Because this massive remodeling of synaptic structures did not occur when all visual input was removed, it likely reflects the activity-dependent establishment of new cortical circuits that serve the recovery of visual responses.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Intrinsic-signal imaging of the LPZ in mouse visual cortex after focal retinal lesions.
Figure 2: Intrinsic imaging of functional recovery in mouse visual cortex after focal retinal lesions.
Figure 3: Structural reorganization in the visual cortex following retinal lesions.
Figure 4: Increased spine dynamics reflect functional reorganization.
Figure 5: Number of new persistent spines increases with functional recovery.


  1. 1

    Shatz, C.J. & Stryker, M.P. Ocular dominance in layer IV of the cat's visual cortex and the effects of monocular deprivation. J. Physiol. (Lond.) 281, 267–283 (1978).

  2. 2

    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).

  3. 3

    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).

  4. 4

    Robertson, D. & Irvine, D.R. Plasticity of frequency organization in auditory cortex of guinea pigs with partial unilateral deafness. J. Comp. Neurol. 282, 456–471 (1989).

  5. 5

    Merzenich, M.M. et al. Topographic reorganization of somatosensory cortical areas 3b and 1 in adult monkeys following restricted deafferentation. Neuroscience 8, 33–55 (1983).

  6. 6

    Kaas, J.H. et al. Reorganization of retinotopic cortical maps in adult mammals after lesions of the retina. Science 248, 229–231 (1990).

  7. 7

    Gilbert, C.D. & Wiesel, T.N. Receptive field dynamics in adult primary visual cortex. Nature 356, 150–152 (1992).

  8. 8

    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).

  9. 9

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

  10. 10

    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).

  11. 11

    Calford, M.B., Wright, L.L., Metha, A.B. & Taglianetti, V. Topographic plasticity in primary visual cortex is mediated by local corticocortical connections. J. Neurosci. 23, 6434–6442 (2003).

  12. 12

    Darian–Smith, C. & Gilbert, C.D. Topographic reorganization in the striate cortex of the adult cat and monkey is cortically mediated. J. Neurosci. 15, 1631–1647 (1995).

  13. 13

    Das, A. & Gilbert, C.D. Long-range horizontal connections and their role in cortical reorganization revealed by optical recording of cat primary visual cortex. Nature 375, 780–784 (1995).

  14. 14

    Giannikopoulos, D.V. & Eysel, U.T. Dynamics and specificity of cortical map reorganization after retinal lesions. Proc. Natl. Acad. Sci. USA 103, 10805–10810 (2006).

  15. 15

    Eysel, U.T. Functional reconnections without new axonal growth in a partially denervated visual relay nucleus. Nature 299, 442–444 (1982).

  16. 16

    Gilbert, C.D. Horizontal integration and cortical dynamics. Neuron 9, 1–13 (1992).

  17. 17

    Hirsch, J.A. & Gilbert, C.D. Long-term changes in synaptic strength along specific intrinsic pathways in the cat visual cortex. J. Physiol. (Lond.) 461, 247–262 (1993).

  18. 18

    Young, J.M. et al. Cortical reorganization consistent with spike timing–, but not correlation-, dependent plasticity. Nat. Neurosci. 10, 887–895 (2007).

  19. 19

    Obata, S., Obata, J., Das, A. & Gilbert, C.D. Molecular correlates of topographic reorganization in primary visual cortex following retinal lesions. Cereb. Cortex 9, 238–248 (1999).

  20. 20

    Van den Bergh, G., Eysel, U.T., Vandenbussche, E., Vandesande, F. & Arckens, L. Retinotopic map plasticity in adult cat visual cortex is accompanied by changes in Ca2+/calmodulin–dependent protein kinase II alpha autophosphorylation. Neuroscience 120, 133–142 (2003).

  21. 21

    Cnops, L., Hu, T.T., Eysel, U.T. & Arckens, L. Effect of binocular retinal lesions on CRMP2 and CRMP4, but not Dyn I and Syt I, expression in adult cat area 17. Eur. J. Neurosci. 25, 1395–1401 (2007).

  22. 22

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

  23. 23

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

  24. 24

    Holtmaat, A., Wilbrecht, L., Knott, G.W., Welker, E. & Svoboda, K. Experience-dependent and cell type–specific spine growth in the neocortex. Nature 441, 979–983 (2006).

  25. 25

    Majewska, A.K., Newton, J.R. & Sur, M. Remodeling of synaptic structure in sensory cortical areas in vivo. J. Neurosci. 26, 3021–3029 (2006).

  26. 26

    Zuo, Y., Yang, G., Kwon, E. & Gan, W.B. Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex. Nature 436, 261–265 (2005).

  27. 27

    Lee, W.C. et al. Dynamic remodeling of dendritic arbors in GABAergic interneurons of adult visual cortex. PLoS Biol. 4, e29 (2006).

  28. 28

    Hofer, S.B., Mrsic-Flogel, T.D., Bonhoeffer, T. & Hübener, M. Prior experience enhances plasticity in adult visual cortex. Nat. Neurosci. 9, 127–132 (2006).

  29. 29

    Chino, Y.M., Smith, E.L., III, Kaas, J.H., Sasaki, Y. & Cheng, H. Receptive-field properties of deafferentated visual cortical neurons after topographic map reorganization in adult cats. J. Neurosci. 15, 2417–2433 (1995).

  30. 30

    Feng, G. et al. Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28, 41–51 (2000).

  31. 31

    Murakami, I., Komatsu, H. & Kinoshita, M. Perceptual filling in at the scotoma following a monocular retinal lesion in the monkey. Vis. Neurosci. 14, 89–101 (1997).

  32. 32

    Horton, J.C. & Hocking, D.R. Monocular core zones and binocular border strips in primate striate cortex revealed by the contrasting effects of enucleation, eyelid suture and retinal laser lesions on cytochrome oxidase activity. J. Neurosci. 18, 5433–5455 (1998).

  33. 33

    Smirnakis, S.M. et al. Lack of long-term cortical reorganization after macaque retinal lesions. Nature 435, 300–307 (2005).

  34. 34

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

  35. 35

    Calford, M.B., Schmid, L.M. & Rosa, M.G. Monocular focal retinal lesions induce short-term topographic plasticity in adult cat visual cortex. Proc. Biol. Sci. 266, 499–507 (1999).

  36. 36

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

  37. 37

    Valverde, F. Apical dendritic spines of the visual cortex and light deprivation in the mouse. Exp. Brain Res. 3, 337–352 (1967).

  38. 38

    Mataga, N., Mizuguchi, Y. & Hensch, T.K. Experience-dependent pruning of dendritic spines in visual cortex by tissue plasminogen activator. Neuron 44, 1031–1041 (2004).

  39. 39

    Knott, G.W., Holtmaat, A., Wilbrecht, L., Welker, E. & Svoboda, K. Spine growth precedes synapse formation in the adult neocortex in vivo. Nat. Neurosci. 9, 1117–1124 (2006).

  40. 40

    Nägerl, U.V., Kostinger, G., Anderson, J.C., Martin, K.A. & Bonhoeffer, T. Protracted synaptogenesis after activity-dependent spinogenesis in hippocampal neurons. J. Neurosci. 27, 8149–8156 (2007).

  41. 41

    Gilbert, C.D. & Wiesel, T.N. Morphology and intracortical projections of functionally characterized neurones in the cat visual cortex. Nature 280, 120–125 (1979).

  42. 42

    Gilbert, C.D. & Wiesel, T.N. Clustered intrinsic connections in cat visual cortex. J. Neurosci. 3, 1116–1133 (1983).

  43. 43

    Martin, K.A. & Whitteridge, D. Form, function and intracortical projections of spiny neurones in the striate visual cortex of the cat. J. Physiol. (Lond.) 353, 463–504 (1984).

  44. 44

    Schuett, S., Bonhoeffer, T. & Hübener, M. Mapping retinotopic structure in mouse visual cortex with optical imaging. J. Neurosci. 22, 6549–6559 (2002).

  45. 45

    Mrsic–Flogel, T.D. et al. Altered map of visual space in the superior colliculus of mice lacking early retinal waves. J. Neurosci. 25, 6921–6928 (2005).

  46. 46

    Denk, W., Strickler, J.H. & Webb, W.W. Two-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990).

Download references


We thank S. Hofer for contributing control data for the Supplementary Discussion. This work was supported by the Max Planck Society (T.K., T.D.M.-F., M.V.A., T.B. and M.H.), the Humboldt Foundation (T.D.M.-F.), the German Research Foundation SFB 509 (U.T.E.) and the Fundação para a Ciência e Tecnologia, Portugal (M.V.A.).

Author information

Correspondence to Mark Hübener.

Supplementary information

Supplementary Text and Figures

Supplementary Discussion (PDF 71 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Keck, T., Mrsic-Flogel, T., Vaz Afonso, M. et al. Massive restructuring of neuronal circuits during functional reorganization of adult visual cortex. Nat Neurosci 11, 1162–1167 (2008) doi:10.1038/nn.2181

Download citation

Further reading