Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Dendrite growth increased by visual activity requires NMDA receptor and Rho GTPases

Abstract

Previous studies suggest that neuronal activity may guide the development of synaptic connections in the central nervous system through mechanisms involving glutamate receptors and GTPase-dependent modulation of the actin cytoskeleton1,2,3,4,5,6,7. Here we demonstrate by in vivo time-lapse imaging of optic tectal cells in Xenopus laevis tadpoles that enhanced visual activity driven by a light stimulus promotes dendritic arbor growth. The stimulus-induced dendritic arbor growth requires glutamate-receptor-mediated synaptic transmission, decreased RhoA activity and increased Rac and Cdc42 activity. The results delineate a role for Rho GTPases in the structural plasticity driven by visual stimulation in vivo.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Visual stimulation in vivo promotes dendritic arbor growth by a glutamate-receptor-dependent mechanism.
Figure 2: Visual system activity regulates branch dynamics in vivo.
Figure 3: Decreased RhoA activity mediates light-induced dendritic arbor growth.
Figure 4: Rac and Cdc42 mediate the light-induced increase in dendrite branch number.

References

  1. Builluart, P. et al. Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation. Nature 392, 823–826 (1998)

    Google Scholar 

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

    ADS  CAS  Article  Google Scholar 

  3. Li, Z., Aizenman, C. D. & Cline, H. T. Regulation of Rho GTPases by crosstalk and neuronal activity in vivo. Neuron 33, 741–750 (2002)

    CAS  Article  Google Scholar 

  4. Li, Z., Van Aelst, L. & Cline, H. T. Rho GTPases regulate distinct aspects of dendritic arbor growth in Xenopus central neurons in vivo. Nature Neurosci. 3, 217–225 (2000)

    CAS  Article  Google Scholar 

  5. 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  Article  Google Scholar 

  6. Fischer, M., Kaech, S., Wagner, U., Brinkhaus, H. & Matus, A. Glutamate receptors regulate actin-based plasticity in dendritic spines. Nature Neurosci. 3, 887–894 (2000)

    CAS  Article  Google Scholar 

  7. 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)

    CAS  Article  Google Scholar 

  8. Wu, G.-Y., Zou, D. J., Rajan, I. & Cline, H. T. Dendritic dynamics in vivo change during neuronal maturation. J. Neurosci. 19, 4472–4483 (1999)

    CAS  Article  Google Scholar 

  9. Rajan, I. & Cline, H. T. Glutamate receptor activity is required for normal development of tectal cell dendrites in vivo. J. Neurosci. 18, 7836–7846 (1998)

    CAS  Article  Google Scholar 

  10. Van Aelst, L. & D'Souza-Schorey, C. Rho GTPases and signaling networks. Genes Dev. 11, 2295–2322 (1997)

    CAS  Article  Google Scholar 

  11. Luo, L. Rho GTPases in neuronal morphogenesis. Nature Rev. Neurosci. 1, 173–180 (2000)

    ADS  CAS  Article  Google Scholar 

  12. Penzes, P. et al. The neuronal Rho-GEF Kalirin-7 interacts with PDZ domain-containing proteins and regulates dendritic morphogenesis. Neuron 29, 229–242 (2001)

    CAS  Article  Google Scholar 

  13. Kim, J. H., Liao, D., Lau, L.-F. & Huganir, R. L. SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family. Neuron 20, 683–691 (1998)

    CAS  Article  Google Scholar 

  14. Zhang, W., Vazquez, L., Apperson, M. & Kennedy, M. B. Citron binds to PSD-95 at glutamatergic synapses on inhibitory neurons in the hippocampus. J. Neurosci. 19, 96–108 (1999)

    CAS  Article  Google Scholar 

  15. Furuyashiki, T. et al. Citron, a Rho-target, interacts with PSD-95/SAP-90 at glutamatergic synapses in the thalamus. J. Neurosci. 19, 109–118 (1999)

    CAS  Article  Google Scholar 

  16. Chen, H. J., Rojas, S. M., Oguni, A. & Kennedy, M. B. A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II. Neuron 20, 895–904 (1998)

    CAS  Article  Google Scholar 

  17. Lawler, S. Regulation of actin dynamics: the LIM kinase connection. Curr. Biol. 9, R800–R802 (1999)

    CAS  Article  Google Scholar 

  18. Aspenstrom, P. Effectors for the Rho GTPases. Curr. Opin. Cell Biol. 11, 95–102 (1999)

    CAS  Article  Google Scholar 

  19. Albertinazzi, C., Gilardelli, D., Paris, S., Longhi, R. & de Curtis, I. Overexpression of a neural-specific rho family GTPase, cRac1B, selectively induces enhanced neuritogenesis and neurite branching in primary neurons. J. Cell Biol. 142, 815–825 (1998)

    CAS  Article  Google Scholar 

  20. Acebes, A. & Ferrus, A. Cellular and molecular features of axon collaterals and dendrites. Trends Neurosci. 23, 557–565 (2000)

    CAS  Article  Google Scholar 

  21. Debant, A. et al. The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac-specific and rho-specific guanine nucleotide exchange factor domains. Proc. Natl Acad. Sci. USA 93, 5466–5471 (1996)

    ADS  CAS  Article  Google Scholar 

  22. Wilk-Blaszczak, M. et al. The monomeric G-proteins Rac1 and/or Cdc42 are required for the inhibition of voltage-dependent calcium current by bradykinin. J. Neurosci. 17, 4094–4100 (1997)

    CAS  Article  Google Scholar 

  23. Djouder, N., Prepens, U., Aktories, K. & Cavalie, A. Inhibition of calcium release-activated calcium current by Rac/Cdc42-inactivating clostridial cytotoxins in RBL cells. J. Biol. Chem. 275, 18732–18738 (2000)

    CAS  Article  Google Scholar 

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

    ADS  CAS  Article  Google Scholar 

  25. Kjoller, L. & Hall, A. Signaling to Rho GTPases. Exp. Cell Res. 253, 166–179 (1999)

    CAS  Article  Google Scholar 

  26. Lendvai, B., Stern, E. A., 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  Article  Google Scholar 

  27. Haas, K., Sin, W.-C., Javaherian, A., Li, Z. & Cline, H. T. Single-cell electroporation for in vivo neuronal gene expression. Neuron 29, 1–9 (2001)

    Article  Google Scholar 

  28. Zhang, L. I., Tao, H. W. & Poo, M. Visual input induces long-term potentiation of developing retinotectal synapses. Nature Neurosci. 3, 708–715 (2000)

    CAS  Article  Google Scholar 

  29. Ruthazer, E. S. & Cline, H. T. Multiphoton imaging of neurons in living tissue: acquisition and analysis of time-lapse morphological data. J. Real-Time Imag. 8, 175–188 (2002)

    Article  Google Scholar 

  30. Leung, T., Chen, X. Q., Manser, E. & Lim, L. The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton. Mol. Cell. Biol. 16, 5313–5327 (1996)

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We thank K. Svoboda, P. O'Brien and B. Burbach for help constructing the two-photon microscope and P. O'Brien for constructing the electronic circuit for visual stimulation. We also thank K. Bronson for technical assistance, J. Duffy for assistance with the figures, and T. Leung and J. Dong for cDNA. We are grateful to L. Van Aelst for discussions, and R. Malinow, J. Dubnau and members of the Cline laboratory for comments on the manuscript. This work was supported by the NIH (H.T.C., K.H., E.S.R) and an endowment from the Charles Robertson Foundation to H.T.C.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hollis T. Cline.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sin, W., Haas, K., Ruthazer, E. et al. Dendrite growth increased by visual activity requires NMDA receptor and Rho GTPases. Nature 419, 475–480 (2002). https://doi.org/10.1038/nature00987

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature00987

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing