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.

  • Letter
  • Published:

Multiple forms of synaptic plasticity triggered by selective suppression of activity in individual neurons

Nature volume 420, pages 414–418 (2002)Cite this article

Abstract

The rules by which neuronal activity causes long-term modification of synapses in the central nervous system are not fully understood. Whereas competitive or correlation-based rules result in local modification of synapses, homeostatic modifications allow neuron-wide changes in synaptic strength, promoting stability1,2. Experimental investigations of these rules at central nervous system synapses have relied generally on manipulating activity in populations of neurons1,3,4,5,6. Here, we investigated the effect of suppressing excitability in single neurons within a network of active hippocampal neurons by overexpressing an inward-rectifier potassium channel. Reducing activity in a neuron before synapse formation leads to a reduction in functional synaptic inputs to that neuron; no such reduction was observed when activity of all neurons was uniformly suppressed. In contrast, suppressing activity in a single neuron after synapses are established results in a homeostatic increase in synaptic input, which restores the activity of the neuron to control levels. Our results highlight the differences between global and selective suppression of activity, as well as those between early and late manipulation of activity.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Overexpression of Kir2.1 in individual neurons depresses excitability.
Figure 2: Suppression of activity before synapse formation leads to a reduction in synaptic input.
Figure 3: Blocking activity uniformly using TTX equalizes synaptic inputs to Kir2.1 and control cells.
Figure 4: Suppression of excitability after synapse formation leads to a homeostatic increase in synaptic inputs.

Similar content being viewed by others

References

  1. Turrigiano, G. G. & Nelson, S. B. Hebb and homeostasis in neuronal plasticity. Curr. Opin. Neurobiol. 10, 358–364 (2000)

    Article  CAS  Google Scholar 

  2. Abbott, L. F. & Nelson, S. B. Synaptic plasticity: taming the beast. Nature Neurosci. 3 Suppl., 1178–1183 (2000)

    Article  CAS  Google Scholar 

  3. Katz, L. C. & Shatz, C. J. Synaptic activity and the construction of cortical circuits. Science 274, 1133–1138 (1996)

    Article  ADS  CAS  Google Scholar 

  4. Rao, A. & Craig, A. M. Activity regulates the synaptic localization of the NMDA receptor in hippocampal neurons. Neuron 19, 801–812 (1997)

    Article  CAS  Google Scholar 

  5. Turrigiano, G. G., Leslie, K. R., Desai, N. S., Rutherford, L. C. & Nelson, S. B. Activity-dependent scaling of quantal amplitude in neocortical neurons. Nature 391, 892–896 (1998)

    Article  ADS  CAS  Google Scholar 

  6. Liao, D., Zhang, X., O'Brien, R., Ehlers, M. D. & Huganir, R. L. Regulation of morphological postsynaptic silent synapses in developing hippocampal neurons. Nature Neurosci. 2, 37–43 (1999)

    Article  CAS  Google Scholar 

  7. Sanes, J. R. & Lichtman, J. W. Development of the vertebrate neuromuscular junction. Ann. Rev. Neurosci. 22, 389–442 (1999)

    Article  CAS  Google Scholar 

  8. Crowley, J. C. & Katz, L. C. Development of ocular dominance columns in the absence of retinal input. Nature Neurosci. 2, 1125–1130 (1999)

    Article  CAS  Google Scholar 

  9. Hubener, M. & Bonhoeffer, T. Eyes wide shut. Nature Neurosci. 2, 1043–1045 (1999)

    Article  CAS  Google Scholar 

  10. Lin, D. M. et al. Formation of precise connections in the olfactory bulb occurs in the absence of odorant-evoked neuronal activity. Neuron 26, 69–80 (2000)

    Article  CAS  Google Scholar 

  11. Zheng, C., Feinstein, P., Bozza, T., Rodriguez, I. & Mombaerts, P. Peripheral olfactory projections are differentially affected in mice deficient in a cyclic nucleotide-gated channel subunit. Neuron 26, 81–91 (2000)

    Article  CAS  Google Scholar 

  12. Zhao, H. & Reed, R. R. X inactivation of the OCNC1 channel gene reveals a role for activity-dependent competition in the olfactory system. Cell 104, 651–660 (2001)

    Article  CAS  Google Scholar 

  13. Luscher, C., Nicoll, R. A., Malenka, R. C. & Muller, D. Synaptic plasticity and dynamic modulation of the postsynaptic membrane. Nature Neurosci. 3, 545–550 (2000)

    Article  CAS  Google Scholar 

  14. Bi, G. Q. & Poo, M. M. Synaptic modification by correlated activity: Hebb's postulate revisited. Ann. Rev. Neurosci. 24, 139–166 (2001)

    Article  CAS  Google Scholar 

  15. Davis, G. W. & Bezprozvanny, I. Maintaining the stability of neural function: a homeostatic hypothesis. Annu. Rev. Physiol. 63, 847–869 (2001)

    Article  CAS  Google Scholar 

  16. Johns, D. C., Marx, R., Mains, R. E., O'Rourke, B. & Marban, E. Inducible genetic suppression of neuronal excitability. J. Neurosci. 19, 1691–1697 (1999)

    Article  CAS  Google Scholar 

  17. Holt, J. R. et al. Functional expression of exogenous proteins in mammalian sensory hair cells infected with adenoviral vectors. J. Neurophysiol. 81, 1881–1888 (1999)

    Article  CAS  Google Scholar 

  18. Xia, Z., Dudek, H., Miranti, C. K. & Greenberg, M. E. Calcium influx via the NMDA receptor induces immediate early gene transcription by a MAP kinase/ERK-dependent mechanism. J. Neurosci. 16, 5425–5436 (1996)

    Article  CAS  Google Scholar 

  19. Craig, A. M., Blackstone, C. D., Huganir, R. L. & Banker, G. Selective clustering of glutamate and GABA receptors opposite synaptic terminals releasing the corresponding neurotransmitters. Proc. Natl Acad. Sci. USA 91, 12373–12377 (1994)

    Article  ADS  CAS  Google Scholar 

  20. O'Brien, R. J. et al. The development of excitatory synapses in cultured spinal neurons. J. Neurosci. 17, 7339–7350 (1997)

    Article  CAS  Google Scholar 

  21. Gomperts, S. N., Carroll, R., Malenka, R. C. & Nicoll, R. A. Distinct roles for ionotropic and metabotropic glutamate receptors in the maturation of excitatory synapses. J. Neurosci. 20, 2229–2237 (2000)

    Article  CAS  Google Scholar 

  22. Cottrell, J. R., Dube, G. R., Egles, C. & Liu, G. Distribution, density, and clustering of functional glutamate receptors before and after synaptogenesis in hippocampal neurons. J. Neurophysiol. 84, 1573–1587 (2000)

    Article  CAS  Google Scholar 

  23. Balice-Gordon, R. J. & Lichtman, J. W. Long-term synapse loss induced by focal blockade of postsynaptic receptors. Nature 372, 519–524 (1994)

    Article  ADS  CAS  Google Scholar 

  24. Betz, W. J. & Bewick, G. S. Optical analysis of synaptic vesicle recycling at the frog neuromuscular junction. Science 255, 200–203 (1992)

    Article  ADS  CAS  Google Scholar 

  25. Li, Z. & Murthy, V. N. Visualizing post-endocytic traffic of synaptic vesicles at hippocampal synapses. Neuron 31, 593–605 (2001)

    Article  CAS  Google Scholar 

  26. Murthy, V. N., Schikorski, T., Stevens, C. F. & Zhu, Y. Inactivity produces increases in neurotransmitter release and synapse size. Neuron 32, 673–682 (2001)

    Article  CAS  Google Scholar 

  27. Bacci, A. et al. Chronic blockade of glutamate receptors enhances presynaptic release and downregulates the interaction between synaptophysin-synaptobrevin-vesicle-associated membrane protein 2. J. Neurosci. 21, 6588–6596 (2001)

    Article  CAS  Google Scholar 

  28. Paradis, S., Sweeney, S. T. & Davis, G. W. Homeostatic control of presynaptic release is triggered by postsynaptic membrane depolarization. Neuron 30, 737–749 (2001)

    Article  CAS  Google Scholar 

  29. 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)

    Article  ADS  CAS  Google Scholar 

  30. Isaac, J. T. R., 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 

Download references

Acknowledgements

We thank E. Marban for the gift of the EGFP–IRES–Kir2.1 construct. We also thank the members of our laboratory for discussion. This work was supported by grants from the National Institutes of Health and the NSF. V.N.M. is a Sloan Foundation Fellow, a Pew Scholar, an EJLB Foundation Scholar and a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator. J.B. is a Grable Investigator of NARSAD.

Author information

Authors and Affiliations

  1. Department of Molecular & Cellular Biology, Harvard University, Cambridge, Massachusetts, 02138, USA

    Juan Burrone, Michael O'Byrne & Venkatesh N. Murthy

Authors
  1. Juan Burrone
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael O'Byrne
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Venkatesh N. Murthy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Venkatesh N. Murthy.

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

Burrone, J., O'Byrne, M. & Murthy, V. Multiple forms of synaptic plasticity triggered by selective suppression of activity in individual neurons. Nature 420, 414–418 (2002). https://doi.org/10.1038/nature01242

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature01242

This article is cited by

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

Advanced 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