Abstract
AMPA receptors (AMPARs) are ionotropic glutamate receptors that play a major role in excitatory neurotransmission. AMPARs are located at both presynaptic and postsynaptic plasma membranes. A huge number of studies investigated the role of postsynaptic AMPARs in the normal and abnormal functioning of the mammalian central nervous system (CNS). These studies highlighted that changes in the functional properties or abundance of postsynaptic AMPARs are major mechanisms underlying synaptic plasticity phenomena, providing molecular explanations for the processes of learning and memory. Conversely, the role of AMPARs at presynaptic terminals is as yet poorly clarified. Accruing evidence demonstrates that presynaptic AMPARs can modulate the release of various neurotransmitters. Recent studies also suggest that presynaptic AMPARs may possess double ionotropic-metabotropic features and that they are involved in the local regulation of actin dynamics in both dendritic and axonal compartments. In addition, evidence suggests a key role of presynaptic AMPARs in axonal pathology, in regulation of pain transmission and in the physiology of the auditory system. Thus, it appears that presynaptic AMPARs play an important modulatory role in nerve terminal activity, making them attractive as novel pharmacological targets for a variety of pathological conditions.
Highlights
Glutamate is the major excitatory neurotransmitter of the central nervous system (CNS)
Puncta immunopositive for synaptophysin and GluA2/3 were located predominantly in laminas III and IV, whereas puncta immunopositive for synaptophysin and GluA4 or GluA2/4 were located predominantly in laminas I and II. These results suggest a role of amino-3hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in the modulation of neurotransmitters’ release by terminals of both myelinated and unmyelinated afferents of dorsal root ganglion (DRG) neurons [20]
TThehseese phenomennaa ccaann ooccccuurriinnvvaarriioouussbbrraaininaarreeaass,ssuucchhaassththeeccoorprpuussstsrtiraitautumm, h, ihpipopcoacmampupsu, s, nucleus accuummbbeennss,pprreeffrroonnttaallccoorrtteexxaannddoolflfaacctotorryybbuulblb[3[311].].AAppootetnentitailacl acvaevaetatotothtehseese studies is tthhaatttthheeyyddiiddnnoottddisistitningguuisishhththeeeefffefecctstsddereirvivininggfrformomthteheacatcivtiavtaiotinonofoAf AMMPAPARsRs from those deriving from the activation of kainate receptors (KARs), because they employed agonists and antagonists that did not allow such distinction. With this caveat in mind, we review here the literature supporting a presynaptic facilitation of DA, NA, 5HT and ACh release induced by AMPARs/KARs
Summary
Glutamate is the major excitatory neurotransmitter of the central nervous system (CNS). Glutamate can cross the blood–brain barrier through high-affinity transport systems for amino acids. Most of brain glutamate is locally synthesized through the glutamine pathway [1]. Glutamine is released by glial cells and taken up by neurons where it is transformed into glutamate through the following two different pathways: by the mitochondrial enzyme glutaminase, or by the transamination of 2-oxoglutarate, an intermediate of the tricarboxylic acid cycle. Vesicular glutamate transport is driven by the membrane potential established by the vacuolar H+ATPase (V-ATPase) across the vesicular membrane [2] and results in high intravesicular concentrations of the neurotransmitter. An action potential-induced Ca2+ increase in axon terminal induces synaptic vesicle (SV) exocytosis, with an ensuing release of glutamate into the synaptic cleft, where it can interact with glutamate receptors
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