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Dendrites are more spiny on mature hippocampal neurons when synapses are inactivated

Nature Neuroscience volume 2, pages 878–883 (1999)Cite this article

An Erratum to this article was published on 01 April 2000

Abstract

Dendrites of CA1 pyramidal neurons in mature rat hippocampal slices were exposed to different levels of synaptic activation. In some slices, synaptic transmission was blocked with glutamate receptor antagonists, sodium and calcium channel blockers and/or a nominally calcium-free medium with high magnesium. In other slices, synapses were activated with low-frequency control stimulation or repeated tetanic stimulation. In slices with blocked synaptic transmission, dendrites were spinier than in either of the activated states. Thus, mature neurons can increase their numbers of spines, possibly compensating for lost synaptic activity.

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Figure 1: Imaging and electrophysiological recording in hippocampal slice preparations.
Figure 2: Two strategies for assessing dendrite spininess.
Figure 3: Dendrite tips were spinier in slices with blocked synaptic transmission than in those under control or tetanus slice conditions.
Figure 4: Dendrite middles are spinier in slices with blocked synaptic transmission than in control or tetanus slice conditions.
Figure 5: Dendrites are also spinier with the selective block of presynaptic or postsynaptic activity.
Figure 6: Electron micrographs from neuropil in area CA1 of adult hippocampal slices.

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References

  1. Gray, E. G. Axo-somatic and axo-dendritic synapses of the cerebral cortex: An electron microscopic study. J. Anat. 93, 420– 433 (1959).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Harris, K. M. & Kater, S. B. Dendritic spines: Cellular specializations imparting both stability and flexibility to synaptic function. Annu. Rev. Neurosci. 17, 341–371 (1994).

    Article  CAS  Google Scholar 

  3. Harris, K. M., Jensen, F. E. & Tsao, B. Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: Implications for the maturation of synaptic physiology and long-term potentiation. J. Neurosci. 12, 2685–2705 (1992).

    Article  CAS  Google Scholar 

  4. Fiala, J. C., Feinberg, M., Popov, V. & Harris, K. M. Synaptogenesis via dendritic filopodia in developing hippocampal area CA1. J. Neurosci. 18, 8900–8911 (1998).

    Article  CAS  Google Scholar 

  5. Papa, M., Bundman, M. C., Greenberger, V. & Segal, M. Morphological analysis of dendritic spine development in primary cultures of hippocampal neurons. J. Neurosci. 15, 1–11 (1995).

    Article  CAS  Google Scholar 

  6. Papa, M. & Segal, M. Morphological plasticity in dendritic spines of cultured hippocampal neurons. Neuroscience 71, 1005–1011 (1996).

    Article  CAS  Google Scholar 

  7. Kossel, A. H., Williams, C. V., Schweizer, M. & Kater, S. B. Afferent innervation influences the development of dendritic branches and spines via both activity-dependent and non-activity-dependent mechanisms. J. Neurosci. 17, 6314– 6324 (1997).

    Article  CAS  Google Scholar 

  8. Halpain, S., Hipolito, A. & Saffer, L. Regulation of F-actin stability in dendritic spines by glutamate receptors and calcineurin. J. Neurosci. 18, 9835–9844 (1998).

    Article  CAS  Google Scholar 

  9. Annis, C. M., O'Dowd, D. K. & Robertson, R. T. Activity-dependent regulation of dendritic spine density on cortical pyramidal neurons in organotypic slice cultures. J. Neurobiol. 25, 1483–1493 (1994).

    Article  CAS  Google Scholar 

  10. McAllister, A. K., Katz, L. C. & Lo, D. C. Neurotrophin regulation of cortical dendritic growth requires activity. Neuron 17, 1057– 1064 (1996).

    Article  CAS  Google Scholar 

  11. Collin, C., Miyaguchi, K. & Segal, M. Dendritic spine density and LTP induction in cultured hippocampal slices. J. Neurophysiol. 77, 1614–1623 (1997).

    Article  CAS  Google Scholar 

  12. Maletic-Savatic, M., Malinow, R. & Svoboda, K. Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. Science 283, 1923–1927 (1999).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  14. Dalva, M. B., Ghosh, A. & Shatz, C. J. Independent control of dendritic and axonal form in the developing lateral geniculate nucleus. J. Neurosci. 14, 3588–3602 (1994).

    Article  CAS  Google Scholar 

  15. Rocha, M. & Sur, M. Rapid acquisition of dendritic spines by visual thalamic neurons after blockade of N-methyl-D-aspartate receptors. Proc. Natl. Acad. Sci. USA 92, 8026– 8030 (1995).

    Article  CAS  Google Scholar 

  16. Bravin, M., Morando, L., Vercelli, A., Rossi, F. & Strata, P. Control of spine formation by electrical activity in the adult rat cerebellum. Proc. Natl. Acad. Sci. USA 96, 1704–1709 ( 1999).

    Article  CAS  Google Scholar 

  17. 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  CAS  Google Scholar 

  18. Woolley, C. S., Gould, E., Frankfurt, M. & McEwen, B. S. Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. J. Neurosci. 10, 4035– 4039 (1990).

    Article  CAS  Google Scholar 

  19. Gould, E., Woolley, C. S., Frankfurt, M. & McEwen, B. S. Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. J. Neurosci. 10, 1286 –1291 (1990).

    Article  CAS  Google Scholar 

  20. Greenough, W. T. & Bailey, C. H. The anatomy of a memory: Convergence of results across a diversity of tests. Trends Neurosci. 11, 142–147 (1988).

    Article  Google Scholar 

  21. Bailey, C. H. & Kandel, E. R. Structural changes accompanying memory storage. Annu. Rev. Physiol. 55, 397–426 (1993).

    Article  CAS  Google Scholar 

  22. Moser, M. B., Trommald, M. & Andersen, P. An increase in dendritic spine density on hippocampal CA1 pyramidal cells following spatial learning in adult rats suggests the formation of new synapses. Proc. Natl. Acad. Sci. USA 91, 12673–12675 (1994).

    Article  CAS  Google Scholar 

  23. Boyer, C., Schikorski, T. & Stevens, C. F. Comparison of hippocampal dendritic spines in culture and in brain. J. Neurosci. 18, 5294– 5300 (1998).

    Article  CAS  Google Scholar 

  24. McKinney, R. A., Capogna, M., Durr, R., Gahwiler, B. H. & Thompson, S. M. Miniature synaptic events maintain dendritic spines via AMPA receptor activation. Nat. Neurosci. 2, 44–49 (1999).

    Article  CAS  Google Scholar 

  25. Harris, K. M. Structure, development, and plasticity of dendritic spines. Curr. Opin. Neurobiol. 9, 343–348 (1999).

    Article  CAS  Google Scholar 

  26. Kirov, S. A., Sorra, K. E. & Harris, K. M. Slices have more synapses than perfusion-fixed hippocampus from both young and mature rats. J. Neurosci. 19, 2876–2886 (1999).

    Article  CAS  Google Scholar 

  27. Dailey, M. E. & Smith, S. J. The dynamics of dendritic structure in developing hippocampal slices. J. Neurosci. 16, 2983–2994 (1996).

    Article  CAS  Google Scholar 

  28. Jensen, F. E. & Harris, K. M. Preservation of neuronal ultrastructure in hippocampal slices using rapid microwave-enhanced fixation. J. Neurosci. Methods 29, 217–230 (1989).

    Article  CAS  Google Scholar 

  29. Sorra, K. E. & Harris, K. M. Stability in synapse number and size at 2 hr after long-term potentiation in hippocampal area CA1. J. Neurosci. 18, 658–671 (1998).

    Article  CAS  Google Scholar 

  30. Trommald, M., Jensen, V. & Andersen, P. Analysis of dendritic spines in rat CA1 pyramidal cells intracellularly filled with a fluorescent dye. J. Comp. Neurol. 353, 260–274 ( 1995).

    Article  CAS  Google Scholar 

  31. Rusakov, D. A. & Stewart, M. G. Quantification of dendritic spine populations using image analysis and a tilting disector. J. Neurosci. Methods 60, 11– 21 (1995).

    Article  CAS  Google Scholar 

  32. Horner, C. H. Plasticity of the dendritic spine. Prog. Neurobiol. 41, 281–321 (1993).

    Article  CAS  Google Scholar 

  33. Chang, F. L. & Greenough, W. T. Lateralized effects of monocular training on dendritic branching in adult split-brain rats. Brain Res. 232, 283–292 ( 1982).

    Article  CAS  Google Scholar 

  34. Andersen, P. & Soleng, A. F. Long-term potentiation and spatial training are both associated with the generation of new excitatory synapses. Brain Res. Brain Res. Rev. 26, 353– 359 (1998).

    Article  CAS  Google Scholar 

  35. Choi, D. W. Glutamate neurotoxicity and diseases of the nervous system. Neuron 1, 623–634 ( 1988).

    Article  CAS  Google Scholar 

  36. Frankenhaeuser, B. & Hodgkin, A. L. The action of calcium on the electrical properties of squid axons. J. Physiol. (Lond.) 137, 218–244 ( 1957).

    Article  CAS  Google Scholar 

  37. Taylor, C. P. & Dudek, F. E. Synchronous neural afterdischarges in rat hippocampal slices without active chemical synapses. Science 218, 810–812 ( 1982).

    Article  CAS  Google Scholar 

  38. Haas, H. L. & Jefferys, J. G. Low-calcium field burst discharges of CA1 pyramidal neurones in rat hippocampal slices. J. Physiol. (Lond.) 354, 185–201 ( 1984).

    Article  CAS  Google Scholar 

  39. Fifkova, E. Actin in the nervous-system. Brain Res. 9, 187–215 (1985).

    Article  CAS  Google Scholar 

  40. Janmey, P. A. Phosphoinositides and calcium as regulators of cellular actin assembly and disassembly. Annu. Rev. Physiol. 56, 169 –191 (1994).

    Article  CAS  Google Scholar 

  41. Fischer, M., Kaech, S., Knutti, D. & Matus, A. Rapid actin-based plasticity in dendritic spines. Neuron 20, 847–854 (1998).

    Article  CAS  Google Scholar 

  42. Nusser, Z. et al. Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus. Neuron 21 , 545–559 (1998).

    Article  CAS  Google Scholar 

  43. Gomperts, S. N., Rao, A., Craig, A. M., Malenka, R. C. & Nicoll, R. A. Postsynaptically silent synapses in single neuron cultures. Neuron 21, 1443– 1451 (1998).

    Article  CAS  Google Scholar 

  44. Petralia, R. S. et al. Selective acquisition of AMPA receptors over postnatal development suggests a molecular basis for silent synapses. Nat. Neurosci. 2, 31–36 ( 1999).

    Article  CAS  Google Scholar 

  45. Shi, S. H. et al. Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science 284 , 1811–1816 (1999).

    Article  CAS  Google Scholar 

  46. Paul, L. A. & Scheibel, A. B. Structural substrates of epilepsy. Adv. Neurol. 44, 775–786 (1986).

    CAS  PubMed  Google Scholar 

  47. Jiang, M., Lee, C. L., Smith, K. L. & Swann, J. W. Spine loss and other persistent alterations of hippocampal pyramidal cell dendrites in a model of early-onset epilepsy. J. Neurosci. 18, 8356–8368 (1998).

    Article  CAS  Google Scholar 

  48. Muller, M., Gahwiler, B. H., Rietschin, L. & Thompson, S. M. Reversible loss of dendritic spines and altered excitability after chronic epilepsy in hippocampal slice cultures. Proc. Natl. Acad. Sci. USA 90, 257–261 ( 1993).

    Article  CAS  Google Scholar 

  49. Drakew, A., Muller, M., Gahwiler, B. H., Thompson, S. M. & Frotscher, M. Spine loss in experimental epilepsy: quantitative light and electron microscopic analysis of intracellularly stained CA3 pyramidal cells in hippocampal slice cultures. Neuroscience . 70, 31–45 ( 1996).

    Article  CAS  Google Scholar 

  50. Segal, M. Morphological alterations in dendritic spines of rat hippocampal neurons exposed to N-methyl-D-aspartate. Neurosci. Lett 193, 73–76 (1995).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank J. Fiala for improving IGL Trace for use with confocal microscopy and for his input on this work. We also thank M. Feinberg and A. Goddard for technical support. This work was supported by NIH grants NS21184, NS33574, MH/DA57351, which is funded jointly by NIMH, NIDA, NASA (K.M.H) and the Mental Retardation Research Center grant P30-HD18655 to Joseph Volpe.

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  1. Division of Neuroscience in the Department of Neurology, Children's Hospital and Harvard Medical School, Enders 260, 300 Longwood Ave., Boston, 02115, Massachusetts, USA

    Sergei A. Kirov & Kristen M. Harris

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Correspondence to Kristen M. Harris.

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Kirov, S., Harris, K. Dendrites are more spiny on mature hippocampal neurons when synapses are inactivated. Nat Neurosci 2, 878–883 (1999). https://doi.org/10.1038/13178

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