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A common origin of synaptic vesicles undergoing evoked and spontaneous fusion


There is a longstanding controversy on the identity of synaptic vesicles undergoing spontaneous versus evoked release. A recent study, introducing a new genetic probe, suggested that spontaneous release is driven by a resting pool of synaptic vesicles refractory to stimulation. We found that cross-depletion of spontaneously or actively recycling synaptic vesicle pools occurred on stimulation in rat hippocampal neurons and identified the recycling pool as a major source of spontaneous release.

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Figure 1: Synaptic vesicles labeled by spontaneous or activity-dependent uptake exhibit identical release kinetics on stimulation.
Figure 2: Synaptic vesicles endocytosed spontaneously and on stimulation recycle equally to the recycling (Rc) and resting (Rs) synaptic vesicle pools.
Figure 3: Synaptic vesicles undergoing spontaneous and activity-dependent recycling originate from the recycling pool.


  1. 1

    Katz, B. & Miledi, R. J. Physiol. (Lond.) 203, 689–706 (1969).

    CAS  Article  Google Scholar 

  2. 2

    Murthy, V.N. & Stevens, C.F. Nat. Neurosci. 2, 503–507 (1999).

    CAS  Article  Google Scholar 

  3. 3

    Lou, X., Scheuss, V. & Schneggenburger, R. Nature 435, 497–501 (2005).

    CAS  Article  Google Scholar 

  4. 4

    Prange, O. & Murphy, T.H. J. Neurosci. 19, 6427–6438 (1999).

    CAS  Article  Google Scholar 

  5. 5

    Sara, Y., Virmani, T., Deak, F., Liu, X. & Kavalali, E.T. Neuron 45, 563–573 (2005).

    CAS  Article  Google Scholar 

  6. 6

    Groemer, T.W. & Klingauf, J. Nat. Neurosci. 10, 145–147 (2007).

    CAS  Article  Google Scholar 

  7. 7

    Fredj, N.B. & Burrone, J. Nat. Neurosci. 12, 751–758 (2009).

    Article  Google Scholar 

  8. 8

    Angleson, J.K. & Betz, W.J. J. Neurophysiol. 85, 287–294 (2001).

    CAS  Article  Google Scholar 

  9. 9

    Adie, E.J. et al. Assay Drug Dev. Technol. 1, 251–259 (2003).

    CAS  Article  Google Scholar 

  10. 10

    Howarth, M. & Ting, A.Y. Nat. Protoc. 3, 534–545 (2008).

    CAS  Article  Google Scholar 

  11. 11

    Martens, H. et al. J. Neurosci. 28, 13125–13131 (2008).

    CAS  Article  Google Scholar 

  12. 12

    Sankaranarayanan, S. & Ryan, T.A. Nat. Neurosci. 4, 129–136 (2001).

    CAS  Article  Google Scholar 

  13. 13

    Miesenböck, G., De Angelis, D.A. & Rothman, J.E. Nature 394, 192–195 (1998).

    Article  Google Scholar 

  14. 14

    Kim, S.H. & Ryan, T.A. Neuron 67, 797–809 (2010).

    CAS  Article  Google Scholar 

  15. 15

    Chung, C., Barylko, B., Leitz, J., Liu, X. & Kavalali, E.T. J. Neurosci. 30, 1363–1376 (2010).

    CAS  Article  Google Scholar 

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We thank K. Hardes for culturing hippocampal neurons, H. Martens (Synaptic Systems) for providing antibodies and E. Neher for critical reading of the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft (Kl 1334/1-1 to J.K.). Y.H. is supported by a stipend from the Max Planck foundation and R.S. by a stipend from the International Max Planck Research School in Neurosciences Göttingen.

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Y.H. and R.S. designed, performed and analyzed the CypHer antibody and spH experiments. M.M. and M.K. designed, performed and analyzed the streptavidin-cypHer experiments. J.K. initialized the project. All of the authors wrote the paper.

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Correspondence to Jürgen Klingauf.

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The authors declare no competing financial interests.

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Supplementary Figures 1–5, Supplementary Notes 1–3, Supplementary Discussion and Supplementary Methods (PDF 496 kb)

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Hua, Y., Sinha, R., Martineau, M. et al. A common origin of synaptic vesicles undergoing evoked and spontaneous fusion. Nat Neurosci 13, 1451–1453 (2010).

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