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Rapid BDNF-induced retrograde synaptic modification in a developing retinotectal system

Nature volume 429, pages 878–883 (2004)Cite this article

Abstract

In cultures of hippocampal neurons, induction of long-term synaptic potentiation or depression by repetitive synaptic activity is accompanied by a retrograde spread of potentiation or depression, respectively, from the site of induction at the axonal outputs to the input synapses on the dendrites of the presynaptic neuron1,2. We report here that rapid retrograde synaptic modification also exists in an intact developing retinotectal system. Local application of brain-derived neurotrophic factor (BDNF) to the Xenopus laevis optic tectum, which induced persistent potentiation of retinotectal synapses, led to a rapid modification of synaptic inputs at the dendrites of retinal ganglion cells (RGCs), as shown by a persistent enhancement of light-evoked excitatory synaptic currents and spiking activity of RGCs. This retrograde effect required TrkB receptor activation, phospholipase Cγ activity and Ca2+ elevation in RGCs, and was accounted for by a selective increase in the number of postsynaptic AMPA-subtype glutamate receptors at RGC dendrites. Such retrograde information flow in the neuron allows rapid regulation of synaptic inputs at the dendrite in accordance to signals received at axon terminals, a process reminiscent of back-propagation algorithm for learning in neural networks3.

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Figure 1: Potentiation of retinotectal synapses by BDNF application at the tectum.
Figure 2: Potentiation of light-evoked excitatory CSCs recorded in RGCs by tectal application of BDNF.
Figure 3: Effects of the tectal application of BDNF on sEPSCs and mEPSCs in RGCs.
Figure 4: Mechanisms underlying the retrograde synaptic modulation by BDNF.

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References

  1. Fitzsimonds, R. M., Song, H. J. & Poo, M. M. Propagation of activity-dependent synaptic depression in simple neural networks. Nature 388, 439–448 (1997)

    Article  ADS  CAS  Google Scholar 

  2. Tao, H. W., Zhang, L. I., Bi, G. Q. & Poo, M. Selective presynaptic propagation of long-term potentiation in defined neural networks. J. Neurosci. 20, 3233–3243 (2000)

    Article  CAS  Google Scholar 

  3. Rumelhart, D. E., Hinton, G. E. & Williams, R. J. Learning representations by back-propagation errors. Nature 323, 533–536 (1986)

    Article  ADS  Google Scholar 

  4. Cohen-cory, S. & Fraser, S. E. BDNF in the development of the visual system of Xenopus. Neuron 12, 747–761 (1994)

    Article  CAS  Google Scholar 

  5. Huang, E. J. & Reichardt, L. F. Neurotrophins: roles in neuronal development and function. Annu. Rev. Neurosci. 24, 677–736 (2001)

    Article  CAS  Google Scholar 

  6. Lohof, A. M. & Poo, M. M. Potentiation of developing neuromuscular synapses by the neurotrophins NT3 and BDNF. Nature 363, 350–353 (1993)

    Article  ADS  CAS  Google Scholar 

  7. Lessmann, V., Gottmann, K. & Heumann, R. BDNF and NT-4/5 enhance glutamatergic synaptic transmission in cultured hippocampal neurones. Neuroreport 6, 21–25 (1994)

    Article  CAS  Google Scholar 

  8. Li, Y. X. et al. Expression of a dominant negative TrkB receptor, T1, reveals a requirement for presynaptic signaling in BDNF-induced synaptic potentiation in cultured hippocampal neurons. Proc. Natl Acad. Sci. USA 95, 10884–10889 (1998)

    Article  ADS  CAS  Google Scholar 

  9. Schinder, A. F., Berninger, B. & Poo, M. M. Postsynaptic target specificity of neurotrophin-induced presynaptic potentiation. Neuron 25, 151–163 (2000)

    Article  CAS  Google Scholar 

  10. Poo, M. M. Neurotrophins as synaptic modulators. Nature Rev. Neurosci. 2, 24–32 (2001)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. Durand, G. M., Kovalchuk, Y. & Konnerth, A. Long-term potentiation and functional synapse induction in developing hippocampus. Nature 381, 71–75 (1996)

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  14. Watson, F. L. et al. Rapid nuclear responses to target-derived neurotrophins require retrograde transport of ligand-receptor complex. J. Neurosci. 19, 7889–7900 (1999)

    Article  CAS  Google Scholar 

  15. von Bartheld, C. S., Byers, M. R., Williams, R. & Bothwell, M. Anterograde transport of neurotrophins and axodendritic transfer in the developing visual system. Nature 379, 830–833 (1996)

    Article  ADS  CAS  Google Scholar 

  16. Ginty, D. D. & Segal, R. A. Retrograde neurotrophin signaling: Trk-ing along the axon. Curr. Opin. Neurobiol. 12, 268–274 (2002)

    Article  CAS  Google Scholar 

  17. Purves, D. Functional and structural changes in mammalian sympathetic neurons following interruption of their axons. J. Physiol. (Lond.) 252, 429–463 (1975)

    Article  CAS  Google Scholar 

  18. Purves, D. Effects of nerve growth factor on synaptic depression after axotomy. Nature 260, 535–536 (1976)

    Article  ADS  CAS  Google Scholar 

  19. Wong, W. T., Faulkner-Jones, B. E., Sanes, J. R. & Wong, R. O. Rapid dendritic remodeling in the developing retina: dependence on neurotransmission and reciprocal regulation by Rac and Rho. J. Neurosci. 20, 5024–5036 (2000)

    Article  CAS  Google Scholar 

  20. Lom, B., Cogen, J., Sanchez, A. L., Vu, T. & Cohen-cory, S. Local and target-derived brain-derived neurotrophic factor exert opposing effects on the dendritic arborization of retinal ganglion cells in vivo. J. Neurosci. 22, 7639–7649 (2002)

    Article  CAS  Google Scholar 

  21. Hartmann, M., Heumann, R. & Lessmann, V. Synaptic secretion of BDNF after high-frequency stimulation of glutamatergic synapses. EMBO J. 20, 5887–5897 (2001)

    Article  CAS  Google Scholar 

  22. Balkowiec, A. & Katz, D. M. Cellular mechanisms regulating activity-dependent release of native brain-derived neurotrophic factor from hippocampal neurons. J. Neurosci. 22, 10399–10407 (2002)

    Article  CAS  Google Scholar 

  23. Chytrova, G. & Johnson, J. E. Spontaneous retinal activity modulates BDNF trafficking in the developing chick visual system. Mol. Cell. Neurosci. 25, 549–557 (2004)

    Article  CAS  Google Scholar 

  24. Constantine-Paton, M., Cline, H. T. & Debski, E. Patterned activity, synaptic convergence, and the NMDA receptor in developing visual pathways. Annu. Rev. Neurosci. 13, 129–154 (1990)

    Article  CAS  Google Scholar 

  25. Wingate, R. J. & Thompson, I. D. Targeting and activity-related dendritic modification in mammalian retinal ganglion cells. J. Neurosci. 14, 6621–6637 (1994)

    Article  CAS  Google Scholar 

  26. Churchland, P. S. & Sejnowski, T. J. The Computational Brain (MIT Press, Cambridge, Massachusetts, 1992)

    MATH  Google Scholar 

  27. Nieuwkoop, P. D. & Faber, J. Normal table of Xenopus laevis, 2nd edn (North Holland, Amsterdam, 1967)

    Google Scholar 

  28. Zhang, L. I., Tao, H. W., Holt, C. E., Harris, W. A. & Poo, M. M. A critical window for cooperation and competition among developing retinotectal synapses. Nature 395, 37–44 (1998)

    Article  ADS  CAS  Google Scholar 

  29. Traynelis, S. F., Silver, R. A. & Cull-Candy, S. G. Estimated conductance of glutamate receptor channels activated during EPSCs at the cerebellar mossy fiber-granule cell synapse. Neuron 11, 279–289 (1993)

    Article  CAS  Google Scholar 

  30. Benke, T. A., Lüthi, A., Isaac, J. T. R. & Collingridge, G. L. Modulation of AMPA receptor unitary conductance by synaptic activity. Nature 393, 793–797 (1998)

    Article  ADS  CAS  Google Scholar 

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Acknowledgements

We thank X. H. Zhang for writing the software of light stimulation and Z. R. Wang for establishing the method of TrkB knockdown of Xenopus tadpoles. This work was supported by grants from the NIH.

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Authors and Affiliations

  1. Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, California, 94720, USA

    Jiu-lin Du & Mu-ming Poo

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  1. Jiu-lin Du
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  2. Mu-ming Poo
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Correspondence to Mu-ming Poo.

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The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Information

Contains supplementary methods (reliability of the noise analysis) and supplementary figure legends. (DOC 29 kb)

Supplementary Figure 1

Dose-dependence of BDNF effects on light-evoked excitatory CSCs in RGCs. (PPT 43 kb)

Supplementary Figure 2

Absence of potentiation of light-evoked CSCs in RGCs following tectal application of NGF or NT-3. (PPT 162 kb)

Supplementary Figure 3

Characterization of sEPSCs and noise analysis under partial blockade of sEPSCs. (PPT 222 kb)

Supplementary Figure 4

Enhanced light-evoked spiking activity of RGCs by tectal application of BDNF. (PPT 91 kb)

Supplementary Figure 5

Enhanced spontaneous spiking activity of RGCs by tectal application of BDNF. (PPT 74 kb)

Supplementary Figure 6

Intracellular inclusion of k252a (200 nM) abolished the retrograde synaptic modification induced by tectal application of BDNF. (PPT 154 kb)

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Du, Jl., Poo, Mm. Rapid BDNF-induced retrograde synaptic modification in a developing retinotectal system. Nature 429, 878–883 (2004). https://doi.org/10.1038/nature02618

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