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Retrograde modulation of presynaptic release probability through signaling mediated by PSD-95–neuroligin

Nature Neuroscience volume 10, pages 186–195 (2007)Cite this article

A Corrigendum to this article was published on 01 February 2008

This article has been updated

Abstract

The structure and function of presynaptic and postsynaptic components of the synapse are highly coordinated. How such coordination is achieved and the molecules involved in this process have not been clarified. Several lines of evidence suggest that presynaptic functionalities are regulated by retrograde mechanisms from the postsynaptic side. We therefore sought postsynaptic mechanisms responsible for trans-synaptic regulation of presynaptic function at excitatory synapses in rat hippocampal CA1 pyramidal neurons. We show here that the postsynaptic complex of scaffolding protein PSD-95 and neuroligin can modulate the release probability of transmitter vesicles at synapse in a retrograde way, resulting in altered presynaptic short-term plasticity. Presynaptic β-neurexin serves as a likely presynaptic mediator of this effect. Our results indicate that trans-synaptic protein-protein interactions can link postsynaptic and presynaptic function.

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Figure 1: Effect of postsynaptic PSD-95 on synaptic transmission.
Figure 2: Postsynaptic PSD-95 regulates release probability in a retrograde way.
Figure 3: Postsynaptic PSD-95 changes presynaptic sensitivity to extracellular Ca2+.
Figure 4: Effect of postsynaptic NLG1 on synaptic transmission.
Figure 5: Interactions between PSD-95 and NLG1 are necessary for both the pre- and postsynaptic effect.
Figure 6: Postsynaptic PSD-95 and NLG regulates the release probability in a retrograde way in CA3–CA3 pyramidal cell synapses.
Figure 7: Reducing presynaptic βNrxn function decreases the release probability.

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Change history

  • 15 January 2008

    In the version of this article initially published, Figure 5e was duplicated in Figure 5o. The authors regret the error,which has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank G.-S. Liu, I. Ehrlich, K. Kobayashi and T. Takahashi for advice, and J.C. Howard for editing. Supported by RIKEN and The Ellison Medical Foundation (Y.H.), a Special Postdoctoral Researchers Fellowship from RIKEN (K.F.), the Howard Hughes Medical Institute (M.S.) and the US National Institutes of Health (R01 NS045014 to P.S.).

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Authors and Affiliations

  1. Department of Brain and Cognitive Sciences, RIKEN-MIT Neuroscience Research Center, The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA

    Kensuke Futai, Myung Jong Kim, Morgan Sheng & Yasunori Hayashi

  2. Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA

    Myung Jong Kim & Morgan Sheng

  3. Laboratory for Neural Architecture, Advanced Technology Development Group, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, 351-0198, Saitama, Japan

    Kensuke Futai & Tsutomu Hashikawa

  4. Department of Physiology and Cellular Biophysics, Center for Neurobiology and Behavior, Columbia University, College of Physicians and Surgeons, P&S 11-511, 630 West 168th Street, New York, 10032, New York, USA

    Peter Scheiffele

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Correspondence to Yasunori Hayashi.

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Supplementary Fig. 1

Confirmation of the efficacy of PSD-95 RNAi construct. (PDF 2306 kb)

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Futai, K., Kim, M., Hashikawa, T. et al. Retrograde modulation of presynaptic release probability through signaling mediated by PSD-95–neuroligin. Nat Neurosci 10, 186–195 (2007). https://doi.org/10.1038/nn1837

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