Visual Cortical Plasticity and Neurotrophic Factors

  • Michela Fagiolini
  • Tommaso Pizzorusso
  • Lamberto Maffei


In a series of landmark experiments, Hubel and Wiesel (1963) demonstrated that the development of primary visual cortex could be disrupted by a variety of sensory perturbation. If a mammal is monocularly deprived (MD) of vision for several days during the early period of postnatal development, the animal permanently becomes ambliopic in that eye (Baker et al., 1974; Boothe et al., 1985; Domenici et al., 1991). The visual acuity of the deprivated eye is decreased and its contrast sensitivity depressed. Most visual cortical neurones become unresponsive to visual stimulation of the deprived eye and the ocular dominance distribution of cells shifts in favour of the eye receiving normal visual input (Giffin and Mitchell, 1978; Harwerth et al., 1989; Domenici et al., 1991a, c). Anatomically, MD performed during the critical period determined the reduction of the territories occupied in the primary visual cortex by the afferents from the deprived laminae of the LGN and the expansion of the territories occupied by the terminals from the non deprived laminae. There is also a shrinkage of the soma size of LGN projection cells in the binocular portion of the deprived laminae (Shatz and Stryker, 1978; LeVay et al., 1980; Guillery and Stelzner, 1970; Sherman et al., 1974).


Nerve Growth Factor Neurotrophic Factor Receptive Field Visual Evoke Potential Lateral Geniculate Nucleus 
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  1. Acheson A., Baker P.A., Alderson R.F., Miller F.D. and Murphy RA. (1991) Detection of Brain-Derived Neurotrophic Factor-like activity in fibroblasts and Schwann cells: inhibition by antibodies to NGF, Neuron 7:265–275.PubMedCrossRefGoogle Scholar
  2. Baker F.H., Grigg P. and von Noorden G.K. (1974) Effects of visual deprivation and strabismus of the response of neurons in the visual cortex of the monkey, including studies on the striate and prestriate cortex in normal animals, Brain Res. 6:185–208.CrossRefGoogle Scholar
  3. Bandtlow C., Heumann R., Schwab M.E. and Thoenen H. (1987) Cellular localization of NGF synthesis by in situ hybridization, EMBO J. 6:891–899.PubMedGoogle Scholar
  4. Berardi N., Domenici L., Parisi V., Pizzorusso T., Cellerino A. and Maffei L. (1993) Monocular deprivation effects in the rat visual cortex and lateral geniculate nucleus are prevented by Nerve Growth Factor (NGF). I. Visual cortex, Proc. R. Soc. Lond. 251:17–23.CrossRefGoogle Scholar
  5. Berardi N., Cellerino A., Domenici L., Fagiolini M., Pizzorusso T., Cattaneo A. and Maffei L. (1993) Monoclonal antibodies to NGF affect the postnatal development of the visual system, Proc. Natl. Acad. Sci. USA (in press).Google Scholar
  6. Berardi N., Cattaneo A., Cellerino A., Domenici L., Fagiolini M., Maffei L. and Pizzorusso T. (1992) Monoclonal antibodies to NGF affects the postnatal development of the rat geniculocortical system, J. Physiol. 452:293P.Google Scholar
  7. Boothe, R.G., Dobson, M.V. and Teller, D.Y. (1985) Postnatal development of vision in human and non human primates, Ann. Rev. Neurosci. 8:495–545.PubMedCrossRefGoogle Scholar
  8. Bozzi, Y., Pizzorusso, T., Cremisi, F., Comelli, M.C., Berardi, N. and Maffei, L. (1993) Monocular deprivation decreases the expression of BDNF mRNA in rat visual cortex. Soc. Neurosci. Abstr. 19:6.Google Scholar
  9. Brokes, J.P., Fields, K.L. and Raff, M.C. (1979) Studies on cultured rat Schwann cells. I: Establishment of purified population from cultures of peripheral nerve, Brain Res. 165:105–118.CrossRefGoogle Scholar
  10. Campbell, F.W. and Maffei, L. (1970) Electrophysiological evidence for the existance of orentation in size detectors in the human visual system, J. Physiol. (Lond.) 207:635–652.Google Scholar
  11. Carmignoto, G., Canella, R., Candeo, P., Comelli, M.C. and Maffei, L. (1993) Effects of NGF on neuronal placicity of the kitten visual cortex, J. Physiol. (Lond.) 464:343–360.Google Scholar
  12. Carmignoto G., Maffei L., Candeo P., Canella R. and Comelli M.C. (1989) Effect of NGF on the survival of retinal ganglion cells after section of the optic nerve J. Neurosci. 9:1263–1272.PubMedGoogle Scholar
  13. Castren, E., Zafra, F., Thoenen, H. and Lindholm, D. (1992) Light regulates expression of brain-derived neurotrophic factor mRNA in rat visual cortex, Proc. Natl. Acad. Sci. USA 89:9444–9448.PubMedCrossRefGoogle Scholar
  14. Cattaneo A., Rapposelli B. and Calissano P. (1988) Three distinct types of monoclonal antibodies after long-term immunization of rats with mouse NGF, J. Neurochem. 50:1003–1010.PubMedCrossRefGoogle Scholar
  15. Daniloff, J.K. (1991) A novel assay fpor the, in vivo study of Schwann cells, Exp. Neurol. 114:140–143.PubMedCrossRefGoogle Scholar
  16. Domenici, L., Berardi, N., Carmigntot, G., Vantini, G. and Maffei, L. (1991) Nerve growth factor prevents the amplyopic effects of monocular deprivation, Proc. Natl Acad. Sci. USA 88:8811–8815.PubMedCrossRefGoogle Scholar
  17. Domenici, L., Cellerino, A. and Maffei, L. (1993) Monocular deprivation effects in the rat visual cortex and lateral geniculate nucleus are prevented by NGF. II. Lateral geniculate nucleus, Proc. R. Soc. Lond B 251:25–31.CrossRefGoogle Scholar
  18. Ferrari G., Fabris M., Polato P., Skaper S.D., Fiori M.G. and Yan Q. (1991) Rat NGF receptor is recognized by Tumor-associated antigen monoclonal antibody 217c, Exp. Neurol. 112:183–194.PubMedCrossRefGoogle Scholar
  19. Fischer W., Bjorklund A. Chen K. and Gage F.H. (1991) NGF improves spatial memory in aged rodents as a function of age, J. Neurosci. 11:1889–1906.PubMedGoogle Scholar
  20. Friden P.M., Walus L.R., Watson P., Doctrow S.R., Kozarich J.W., Backman C., Bergman H., Hoffer B., Bloom F. and Granholm A.C. (1993) Blood-brian barrier penetration and in vivo activity of an NGF conjugate, Science 259:373–377.PubMedCrossRefGoogle Scholar
  21. Friedman B., Scherer S.S., Rudge J.S., Helgren M., Morrisey D., McClain J., Wangf D., Wiegand S.J., Furth M.E., Lindsay R.M. and Ip N.Y. (1992) Regulation of Ciliary Neurotrophic Factor expressio in myelin-related Schwann cells in vivo, Neuron 9:295–305.PubMedCrossRefGoogle Scholar
  22. Giffin F. and Mitchell D.E. (1978) The rate of recovery of vision after early monocular deprivation in kittens, J. Physiol. (Lond.) 274:511–537.Google Scholar
  23. Guillery R.W. and Stelzner D.J. (1970) The differential effects of unilateral lid closure upon the monocular and binocular segments of the dorsal genicualte nucleus in the cat, J. Comp. Neurol 139:413–422.PubMedCrossRefGoogle Scholar
  24. Hanker J.S., Yates P.E., Metz C.B. and Rustioni A. (1977) A new specific, sensitive and non-carcinogenic reagent for the demonstration of horseradish peroxidase, Histochem. J. 9:789–792.PubMedCrossRefGoogle Scholar
  25. Harwerth R.S., Smith E.L. III, Crawford M.L.J. and von Noorden G.K. (1989) the effects of reverse monocular deprivation in monkeys. I: Psychophysical experiments, Exp. Brain Res. 74:327–337.PubMedCrossRefGoogle Scholar
  26. Hefti F. (1986) NGF promotes survival of septal colinergic neurons after fimbrial transections, J. Neurosci. 6:2155–2162.PubMedGoogle Scholar
  27. Hubel D. H. and Wiesel T. N. (1963) Receptive fields of cells in the striate cortex of very young, visually inexperienced kittens, J. Neurophysiol. 26:994–1002.PubMedGoogle Scholar
  28. Hubel D. H. and Wiesel T. N. (1962) Receptive fields, binocualr interactionand functional architecturein the cat’s visual cortex, J Physiol (Lond) 160:106–154.Google Scholar
  29. Kawaja M.D., Rosenberg M.B., Yoshida K. and Gage F.H. (1992) Somatic gene transfer of NGF promotes the survival of axomized septal neurons and the regeneration of their axons in adult rats, J. Neurosci. 12:2849–2864.PubMedGoogle Scholar
  30. Knusel B., Beck K.D., Winslow J.W., Rosenthal A., Burton L.E., Widmer H.R., Nikolics K. and Hefti F. (1992) BDNF administration protects basal forebrain cholinergic but not nigral dopaminergic neurons from degenerative changes after axotomy in the adult rat brain, J. Neurosci. 12:4391–4402.PubMedGoogle Scholar
  31. Kromer L.F. and Combrooks C.J. (1985) Transplants of Schwann cell cultures promote axonal regeneration in the adult mammalian brain, Proc. Natl. Acad. Sci. USA 82:6330–6334.PubMedCrossRefGoogle Scholar
  32. Lapchak P.A., Beck K.D., Araujo D.M., Irwin I., Langston J.W. and Hefti F. (1993) Chronic intranigral administration of BDNF producers striatal dopaminergic hypofunctioin in unlesioned adult rats and fails to attenuate the decline of striatal dopaminergic function following medial forebrain bundle transection, Neurosci. 53:639–650.CrossRefGoogle Scholar
  33. Large T.H., Bodary S.C., Clegg D.O., Weskamp G., Otten U. and Reichardt L. F. (1986) Nerve growth factor gene expression in the developing rat brain, Science 234:352–355.PubMedCrossRefGoogle Scholar
  34. LeVay S., Wiesel T.N. and Hubel D.H. (1980) The development of ocular dominance columns in normal and visually deprived monkeys, J. Comp. Neurol. 191:1–51.PubMedCrossRefGoogle Scholar
  35. Maffei L., Carmignoto G., Perry V.H., Candeo P. and Ferrari G. (1990) Schwann cells promote the survival of retinal ganglion cells after optic nerve section, Proc. Natl. Acad. Sci. USA 87:1855–1859.PubMedCrossRefGoogle Scholar
  36. Maffei L., Berardi N., Domenici L., Parisi V. and Pizzorusso T. (1992) Nerve Growth Factor (NGF) prevents the shift in ocular dominance distribution of visual cortical neurons in monocularly deprived rats, J. Neurosci. 12:4651–4662.PubMedGoogle Scholar
  37. Matsuoka I., Meyer M. and Thoenen H. (1991) Cell-type-specific regulation of NGF synthesis in non-neuronal cells: comparison of Schwann cells with other cell types, J. Neurosci. 11:3165–3177.PubMedGoogle Scholar
  38. Messersmith D.J., Fabrazzo M., Mocchetti I. and Kromer L.F. (1991) Effects of sciatic nerve transplants after fimbriafornixlesion: examination of the role of NGF, Brain Res. 557:293–297.PubMedCrossRefGoogle Scholar
  39. Pamavelas J.G., Burne R.A. and Lin C.S. (1981) Receptive field properties of neurons in the visual cortex of the rat, Neurosci. Lett. 27:291–296.CrossRefGoogle Scholar
  40. Phelps C.H., Gage F.H., Growdon J.H., Hefti F., Harbaugh R., Johnston M.V., Kachaturian Z.S., Mobley W.C., Price D.L., Raskind M., Simpkins J., Thal L.J. and Woodcock J. (1989) Potential use of NGF to treat Alzheimer’s disease, Neurobiol. Aging 10:205–207.PubMedCrossRefGoogle Scholar
  41. Pizzorusso T., Fagiolini M., Fabris M., Ferrari G. and Maffei L. (1994) Schwann cells transplanted in the lateral ventricles prevents the functional and anatomical effects of monocular deprivation in the rat, Proc. Natl. Acad. Sci. USA 91:2572–2576.PubMedCrossRefGoogle Scholar
  42. Reese B.E. (1988) “Hidden lamination” in the dorsal lateral geniculate nucleus: the functional organization of this thalamic region in the rat, Brain Res Rev. 13:119–137.CrossRefGoogle Scholar
  43. Reese B.E. and Jeffery G. (1983) Crossed and uncrossed visual topography in dorsal lateral genicualte nucleus of pigmented rat, J. Neurophysiol. 49:877–885.PubMedGoogle Scholar
  44. Schnell L. and Schwab (1990) Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors, Nature 343:269–272.PubMedCrossRefGoogle Scholar
  45. Shatz C.J. and Stryker M.P. (1978) Ocular dominance in layer IV of the cats visual cortex and the effects of visual deprivation, J. Physiol. 281:267–283.PubMedGoogle Scholar
  46. Sherman S.M., Guillery R.W., Kaas J.H. and Sanderson K.J. (1974) Behavioral, electrophysiological and morphological studies of binocular competition in the development of the geniculo-cortical pathways of cats, J. Comp. Neurol. 158:1–18.PubMedCrossRefGoogle Scholar
  47. Sloan D.J., Wood M.J. and Charlton H.M. (1991) The immune response to intracerebral neural grafts, Trends Neurosci. 14:341–346.PubMedCrossRefGoogle Scholar
  48. Thoenen H. (1991) The changing scene of neurotrophic factors, Trends Neurosci. 14:165–170.PubMedCrossRefGoogle Scholar
  49. Thurlow G. A. and Cooper R. M. (1988) Metabolic activity in striate and extrastriate cortex of the hooded rat: controlateral and ipsilateral eye input, J. Comp. Neurol. 274:595–607.PubMedCrossRefGoogle Scholar
  50. Wiesel T. N. and Hubel D. H. (1963) Single-cell responses in striate cortex of kittens deprived of in one eye, J. Neurophysiol. 26:1003–1017.PubMedGoogle Scholar
  51. Wiesenfeld Z. and Komel E. (1975) Receptive fields of single cells in the visual cortex of the hooded rat, Brain Res. 94:401–412.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Michela Fagiolini
    • 1
  • Tommaso Pizzorusso
    • 1
  • Lamberto Maffei
    • 1
    • 2
  1. 1.Scuola Normale SuperiorePisaItaly
  2. 2.Istituto Neurofisiologia CNRPisaItaly

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