Nonsynaptic Receptors for GABA and Glutamate

The concept of nonsynaptic communication between neurons, once a heretic idea, has become a self-evident fact during the almost forty years since its original discovery [1]. In this review we investigate whether the archetypical synaptic transmitters of the central nervous system, Glu and GABA, can operate via nonsynaptic transmission. While experimental data supporting the general concept of nonsynaptic transmission has been progressively accumulating during these years, most of the evidence regarding nonsynaptic transmission by Glu and GABA are results of the last decade. In this paper we collect evidence for different forms of nonsynaptic transmission by the Gluergic and GABAergic system. We investigate two theoretical predictions of the concept of nonsynaptic transmission in the light of recent progress in the field: i) since extrasynaptic receptors experience a lower concentration of agonist, they are likely to have higher affinity for the agonist ii) extrasynaptic receptors are expected to be more important pharmacological targets.