Abstract
SummaryElectric 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.
Highlights
Electric currents flowing through synaptic receptor channels can give rise to substantial electric fields inside the narrow synaptic cleft (Savtchenko and Rusakov, 2007), a phenomenon predicted analytically decades ago by Eccles and Jaeger (1958)
To optimize voltage-clamp conditions, here, we focus on synapses between cerebellar mossy fibers (MFs) and granule cells (GCs), one of the smallest, electrically compact central neurons (Diwakar et al, 2009) receiving only four excitatory inputs (Figure 1A)
Postsynaptic Depolarization Retards Escape of Glutamate from the Synaptic Cleft The decay constant of AMPAR EPSCs evoked in GCs by MF stimulation increased monotonically with cell depolarization (Figure 1B)
Summary
Electric currents flowing through synaptic receptor channels can give rise to substantial electric fields inside the narrow synaptic cleft (Savtchenko and Rusakov, 2007), a phenomenon predicted analytically decades ago by Eccles and Jaeger (1958). We previously found that synaptic currents could influence intracleft glutamate diffusion at CA3-CA1 synapses in the hippocampus (Sylantyev et al, 2008). This phenomenon could only reveal itself as a slowdown of the EPSC decay, or an increase in the intracleft concentration of released glutamate, upon sustained postsynaptic depolarization above zero. Such depolarization is unlikely to happen in vivo. The adaptive physiological significance of electric fields interacting with glutamate inside the synaptic cleft remains uncertain
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