Extrasynaptic and postsynaptic receptors in glycinergic and GABAergic neurotransmission: a division of labor?

Emilie Muller

doi:10.3389/neuro.02.003.2008

Abstract

Glycine and GABA mediate inhibitory neurotransmission in the spinal cord and central nervous system. The general concept of neurotransmission is now challenged by the contribution of both phasic activation of postsynaptic glycine and GABAA receptors (GlyRs and GABAARs, respectively) and tonic activity of these receptors located at extrasynaptic sites. GlyR and GABAAR kinetics depend on several parameters, including subunit composition, subsynaptic localization and activation mode. Postsynaptic and extrasynaptic receptors display different subunit compositions and are activated by fast presynaptic and slow paracrine release of neurotransmitters, respectively. GlyR and GABAAR functional properties also rely on their aggregation level, which is higher at postsynaptic densities than at extrasynaptic loci. Finally, these receptors can co-aggregate at mixed inhibitory postsynaptic densities where they cross-modulate their activity, providing another parameter of functional complexity. GlyR and GABAAR density at postsynaptic sites results from the balance between their internalization and insertion in the plasma membrane, but also on their lateral diffusion from and to the postsynaptic loci. The dynamic exchange of receptors between synaptic and extrasynaptic sites and their functional adaptation in terms of kinetics point out a new adaptive process of inhibitory neurotransmission.

Highlights

The idea that, in the adult, non-synaptic release of neurotransmitters occurs in addition to classical release from presynaptic terminals, gains more significance in recent years
Recent findings demonstrated that the density of receptors at postsynaptic sites does not solely depend on the balance between their internalization and insertion in the plasma membrane, and on their lateral diffusion from and to the postsynaptic loci (Bruneau and Akaaboune, 2006; Kneussel and Loebrich, 2007; Triller and Choquet, 2005)
While this has been first demonstrated for N-Methyl-D-Aspartate receptors (NMDARs) at glutamatergic excitatory synapses, it was recently shown to occur at inhibitory synapses

Summary

Introduction

The idea that, in the adult, non-synaptic release of neurotransmitters occurs in addition to classical release from presynaptic terminals, gains more significance in recent years. March 2008 | Volume 1 | Article 3 | www.frontiersin.org recent findings indicate that the co-activation of GlyRs and GABAARs at mixed inhibitory synapses does not display a summation of currents mediated by both receptor subtypes, resulting from functional cross-talk between these co-aggregated postsynaptic receptors.

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