Spike-Driven Glutamate Electrodiffusion Triggers Synaptic Potentiation via a Homer-Dependent mGluR-NMDAR Link

Sergiy Sylantyev, Leonid P. Savtchenko, Yaroslav Ermolyuk, Piotr Michaluk, Dmitri A. Rusakov*

*Corresponding author for this work

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Electric fields of synaptic currents can influence diffusion of charged neurotransmitters, such as glutamate, in the synaptic cleft. However, this phenomenon has hitherto been detected only through sustained depolarization of large principal neurons, and its adaptive significance remains unknown. Here, we find that in cerebellar synapses formed on electrically compact granule cells, a single postsynaptic action potential can retard escape of glutamate released into the cleft. This retardation boosts activation of perisynaptic group I metabotropic glutamate receptors (mGluRs), which in turn rapidly facilitates local NMDA receptor currents. The underlying mechanism relies on a Homer-containing protein scaffold, but not GPCR- or Ca2+-dependent signaling. Through the mGluR-NMDAR interaction, the coincidence between a postsynaptic spike and glutamate release triggers a lasting enhancement of synaptic transmission that alters the basic integrate-and-spike rule in the circuitry. Our results thus reveal an electrodiffusion-driven synaptic memory mechanism that requires high-precision coincidence detection suitable for high-fidelity circuitries.
Original languageEnglish
Pages (from-to)528-541
Number of pages14
JournalNeuron
Volume77
Issue number3
DOIs
Publication statusPublished - 6 Feb 2013

Fingerprint Dive into the research topics of 'Spike-Driven Glutamate Electrodiffusion Triggers Synaptic Potentiation via a Homer-Dependent mGluR-NMDAR Link'. Together they form a unique fingerprint.

  • Cite this

    Sylantyev, S., Savtchenko, L. P., Ermolyuk, Y., Michaluk, P., & Rusakov, D. A. (2013). Spike-Driven Glutamate Electrodiffusion Triggers Synaptic Potentiation via a Homer-Dependent mGluR-NMDAR Link. Neuron, 77(3), 528-541. https://doi.org/10.1016/j.neuron.2012.11.026