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

Kensuke Futai, Myung Jong Kim, Tsutomu Hashikawa, Peter Scheiffele, Morgan Sheng, Yasunori Hayashi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

234 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)186-195
Number of pages10
JournalNature neuroscience
Volume10
Issue number2
DOIs
StatePublished - Feb 2007

Funding

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.).

ASJC Scopus subject areas

  • General Neuroscience

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