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Synaptic dynamism measured over minutes to months: age-dependent decline in an autonomic ganglion

Abstract

Naturally occurring rearrangements of synaptic terminals are common in the nervous systems of young mammals, but little is known about their incidence in adults. Using transgenic mice that express yellow fluorescent protein (YFP) in axons, we repeatedly imaged nerve terminals in the parasympathetic submandibular ganglion. We found that the pattern of synaptic branches underwent significant rearrangements over several weeks in young adult mice. In older mice, rearrangements were less common, and synaptic patterns on individual neurons were recognizable for many months to years. Axonal branches frequently retracted or extended on a time scale of minutes in young adult mice, but seldom in mature animals. These results provide direct evidence for a decrease in plasticity of interneuronal connections as animals make the transition from young adulthood to middle age. The long-term stability of synaptic patterns could provide a structural basis for the persistence of memory in the adult nervous system.

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Figure 1: YFP labeling of preganglionic axons and synaptic boutons in the submandibular ganglion.
Figure 2: Overall stability of synaptic connections as well as some local remodeling over weeks to months.
Figure 3: Imaging ganglion cells over months or years showed stability of synaptic patterns.
Figure 4: Distribution of synaptic connections is more stable in mature animals than in young adults.
Figure 5: In vivo time-lapse recording of rapid change of synaptic terminal arbors in young mice.

References

  1. Hubel, D.H., Wiesel, T.N. & LeVay, S. Plasticity of ocular dominance columns in monkey striate cortex. Philos. Trans. R. Soc. Lond. B Biol. Sci. 278, 377–409 (1977).

    CAS  Article  Google Scholar 

  2. Rakic, P., Bourgeois, J.P., Eckenhoff, M.F., Zecevic, N. & Goldman-Rakic, P.S. Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. Science 11, 232–235 (1986).

    Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  4. Lichtman, J.W. & Colman, H. Synapse elimination and indelible memory. Neuron 25, 269–278 (2000).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  6. Darian-Smith, C. & Gilbert, C.D. Axonal sprouting accompanies functional reorganization in adult cat striate cortex. Nature 368, 737–740 (1994).

    CAS  Article  Google Scholar 

  7. Jones, T.A., Klintsova, A.Y., Kilman, V.L., Sirevaag, A.M. & Greenough, W.T. Induction of multiple synapses by experience in the visual cortex of adult rats. Neurobiol. Learn. Mem. 68, 13–20 (1997).

    CAS  Article  Google Scholar 

  8. Kilgard, M.P. & Merzenich, M.M. Plasticity of temporal information processing in the primary auditory cortex. Nat. Neurosci. 1, 727–731 (1998).

    CAS  Article  Google Scholar 

  9. Florence, S.L., Taub, H.B. & Kaas, J.H. Large-scale sprouting of cortical connections after peripheral injury in adult macaque monkeys. Science 282, 1117–1121 (1998).

    CAS  Article  Google Scholar 

  10. Jones, E.G. & Pons, T.P. Thalamic and brainstem contributions to large-scale plasticity of primate somatosensory cortex. Science 282, 1121–1125 (1998).

    CAS  Article  Google Scholar 

  11. Bao, S., Chan, V.T. & Merzenich, M.M. Cortical remodeling induced by activity of ventral tegmental dopamine neurons. Nature 412, 79–83 (2001).

    CAS  Article  Google Scholar 

  12. Knott, G.W., Quairiaux, C., Genoud, C. & Welker, E. Formation of dendritic spines with GABAergic synapses induced by whisker stimulation in adult mice. Neuron 34, 265–273 (2002).

    CAS  Article  Google Scholar 

  13. Bertoni-Freddari, C. et al. Synaptic structural dynamics and aging. Gerontology 42, 170–180 (1996).

    CAS  Article  Google Scholar 

  14. Desai, N.S., Cudmore, R.H., Nelson, S.B. & Turrigiano, G.G. Critical periods for experience-dependent synaptic scaling in visual cortex. Nat. Neurosci. 5, 783–789 (2002).

    CAS  Article  Google Scholar 

  15. Sawaki, L., Yaseen, Z., Kopylev, L. & Cohen, L.G. Age-dependent changes in the ability to encode a novel elementary motor memory. Ann. Neurol. 53, 521–524 (2003).

    Article  Google Scholar 

  16. Grutzendler, J., Kasthuri, N. & Gan, W.B. Long-term dendritic spine stability in the adult cortex. Nature 420, 812–816 (2002).

    CAS  Article  Google Scholar 

  17. Daw, N.W. Critical periods and amblyopia. Arch. Ophthalmol. 116, 502–505 (1998).

    CAS  Article  Google Scholar 

  18. Lichtman, J.W., Magrassi, L. & Purves, D. Visualization of neuromuscular junctions over periods of several months in living mice. J. Neurosci. 7, 1215–1222 (1987).

    CAS  Article  Google Scholar 

  19. Balice-Gordon, R.J. & Lichtman, J.W. In vivo visualization of the growth of pre- and postsynaptic elements of neuromuscular junctions in the mouse. J. Neurosci. 10, 894–908 (1990).

    CAS  Article  Google Scholar 

  20. Walsh, M.K. & Lichtman, J.W. In vivo time-lapse imaging of synaptic takeover associated with naturally occurring synapse elimination. Neuron 37, 67–73 (2003).

    CAS  Article  Google Scholar 

  21. Purves, D, & Hadley, R.D. Changes in the dendritic branching of adult mammalian neurones revealed by repeated imaging in situ. Nature 315, 404–406 (1985).

    CAS  Article  Google Scholar 

  22. Purves, D., Hadley, R.D. & Voyvodic, J.T. Dynamic changes in the dendritic geometry of individual neurons visualized over periods of up to three months in the superior cervical ganglion of living mice. J. Neurosci. 6, 1051–1060 (1986).

    CAS  Article  Google Scholar 

  23. Purves, D., Voyvodic, J.T., Magrassi, L. & Yawo, H. Nerve terminal remodeling visualized in living mice by repeated examination of the same neuron. Science 238, 1122–1126 (1987).

    CAS  Article  Google Scholar 

  24. Feng, G. et al. Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28, 41–51 (2000).

    CAS  Article  Google Scholar 

  25. Trachtenberg, J.T. et al. Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420, 788–794 (2002).

    CAS  Article  Google Scholar 

  26. Purves, D. & Lichtman, J.W. Synaptic sites on reinnervated nerve cells visualized at two different times in living mice. J. Neurosci. 7, 1492–1497 (1987).

    CAS  Article  Google Scholar 

  27. Lichtman, J.W. The reorganization of synaptic connexions in the rat submandibular ganglion during post-natal development. J. Physiol. 273, 155–177 (1977).

    CAS  Article  Google Scholar 

  28. Snider, W.D. The dendritic complexity and innervation of submandibular neurons in five species of mammals. J. Neurosci. 7, 1760–1768 (1987).

    CAS  Article  Google Scholar 

  29. Snider, W.D. & Lichtman, J.W. Are neurotrophins synaptotrophins? Mol. Cell. Neurosci. 7, 433–442 (1996).

    CAS  Article  Google Scholar 

  30. McEwen, B.S. Stress and hippocampal plasticity. Annu. Rev. Neurosci. 22, 105–122 (1999).

    CAS  Article  Google Scholar 

  31. Zhang, W. & Benson D.L. Stages of synapse development defined by dependence on F-actin. J. Neurosci. 21, 5169–5181 (2001).

    CAS  Article  Google Scholar 

  32. Eaton, B.A., Fetter, R.D. & Davis, G.W. Dynactin is necessary for synapse stabilization. Neuron 34, 729–741 (2002).

    CAS  Article  Google Scholar 

  33. Bruses, J.L. Cadherin-mediated adhesion at the interneuronal synapse. Curr. Opin. Cell Biol. 12, 593–597 (2000).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

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Acknowledgements

We thank H. Suk-Woo for help with data analysis. This work was supported by grants from the US National Institutes of Health (NIH) to J.W.L. and J.R.S. W-B.G. and E.K. were supported by grants to W-B.G. from the NIH (R01 NS41846-01) and the Ellison Foundation. Support from the Bakewell NeuroImaging Fund is gratefully acknowledged.

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Correspondence to Jeff W Lichtman.

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Gan, WB., Kwon, E., Feng, G. et al. Synaptic dynamism measured over minutes to months: age-dependent decline in an autonomic ganglion. Nat Neurosci 6, 956–960 (2003). https://doi.org/10.1038/nn1115

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