Glutamate acts on postsynaptic glutamate receptors to mediate excitatory communication between neurons. The discovery that additional presynaptic glutamate receptors can modulate neurotransmitter release has added complexity to the way we view glutamatergic synaptic transmission. Here we review evidence of a physiological role for presynaptic glutamate receptors in neurotransmitter release. We compare the physiological roles of ionotropic and metabotropic glutamate receptors in short- and long-term regulation of synaptic transmission. Furthermore, we discuss the physiological conditions that are necessary for their activation, the source of the glutamate that activates them, their mechanisms of action and their involvement in higher brain function.
Histological and ultrastructural localization of the kainate receptor subunits, KA2 and GluR6/7, in the rat nervous system using selective antipeptide antibodies
Target-cell-specific concentration of a metabotropic glutamate receptor in the presynaptic active zone
Regional and laminar differences in synaptic localization of NMDA receptor subunit NR1 splice variants in rat visual cortex and hippocampus
High-resolution immunogold localization of AMPA type glutamate receptor subunits at synaptic and non-synaptic sites in rat hippocampus
Tonic facilitation of glutamate release by presynaptic N-methyl-D-aspartate autoreceptors in the entorhinal cortex
Use-dependent increases in glutamate concentration activate presynaptic metabotropic glutamate receptors
Presynaptic modulation by metabotropic glutamate receptors of excitatory and inhibitory synaptic inputs to hypothalamic magnocellular neurons
mGluR II agonist inhibition of LTP induction, and mGluR II antagonist inhibition of LTD induction, in the dentate gyrus in vitro
Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma
Modulation of pre- and postsynaptic calcium dynamics by ionotropic glutamate receptors at a plastic synapse
Calcium-dependent mechanisms involved in presynaptic long-term depression at the hippocampal mossy fibre-CA3 synapse
Neuronal and glial localization of NR1 and NR2A/B subunits of the NMDA receptor in the human cerebral cortex
Synaptically released glutamate reduces gamma-aminobutyric acid (GABA)ergic inhibition in the hippocampus via kainate receptors
Long-term depression in hippocampal interneurons: joint requirement for pre- and postsynaptic events
Dynamic control of presynaptic Ca(2+) inflow by fast-inactivating K(+) channels in hippocampal mossy fiber boutons
Kainate receptors are involved in short- and long-term plasticity at mossy fiber synapses in the hippocampus
Presynaptic kainate receptor mediation of frequency facilitation at hippocampal mossy fiber synapses
G protein betagamma subunit-mediated presynaptic inhibition: regulation of exocytotic fusion downstream of Ca2+ entry
Distribution of metabotropic glutamate receptor mGluR3 in the mouse CNS: differential location relative to pre- and postsynaptic sites
Direct presynaptic regulation of GABA/glycine release by kainate receptors in the dorsal horn: an ionotropic mechanism
Retrograde modulation of transmitter release by postsynaptic subtype 1 metabotropic glutamate receptors in the rat cerebellum
A presynaptic kainate receptor is involved in regulating the dynamic properties of thalamocortical synapses during development
Functional expression of AMPA receptors on central terminals of rat dorsal root ganglion neurons and presynaptic inhibition of glutamate release
Enrichment of mGluR7a in the presynaptic active zones of GABAergic and non-GABAergic terminals on interneurons in the rat somatosensory cortex
Role for cAMP and protein phosphatase in the presynaptic expression of mouse hippocampal mossy fibre depotentiation
Reduction of excitatory postsynaptic responses by persistently active metabotropic glutamate receptors in the hippocampus
A role for Ca2+ stores in kainate receptor-dependent synaptic facilitation and LTP at mossy fiber synapses in the hippocampus
Presynaptic kainate receptors impart an associative property to hippocampal mossy fiber long-term potentiation
Pre-synaptic kainate receptors in GABAergic and glutamatergic axon terminals in the monkey globus pallidus
Intracellular astrocyte calcium waves in situ increase the frequency of spontaneous AMPA receptor currents in CA1 pyramidal neurons
Tonic activity of metabotropic glutamate receptors is involved in developmental modification of short-term plasticity in the neocortex
Retrograde activation of presynaptic NMDA receptors enhances GABA release at cerebellar interneuron-Purkinje cell synapses
AMPA receptor-mediated presynaptic inhibition at cerebellar GABAergic synapses: a characterization of molecular mechanisms.
Endocannabinoid-independent retrograde signaling at inhibitory synapses in layer 2/3 of neocortex: involvement of vesicular glutamate transporter 3
Glial glutamate transporters limit spillover activation of presynaptic NMDA receptors and influence synaptic inhibition of Purkinje neurons
Lack of the metabotropic glutamate receptor subtype 7 selectively impairs short-term working memory but not long-term memory
Presynaptic localization of an AMPA-type glutamate receptor in corticostriatal and thalamostriatal axon terminals
The metabotropic glutamate receptor mGluR3 is critically required for hippocampal long-term depression and modulates long-term potentiation in the dentate gyrus of freely moving rats
Neurosteroid-induced plasticity of immature synapses via retrograde modulation of presynaptic NMDA receptors
G protein betagamma directly regulates SNARE protein fusion machinery for secretory granule exocytosis
Unmasking group III metabotropic glutamate autoreceptor function at excitatory synapses in the rat CNS
Endogenous activation of kainate receptors regulates glutamate release and network activity in the developing hippocampus
Modulation of presynaptic Ca2+ entry by AMPA receptors at individual GABAergic synapses in the cerebellum
Endogenous activation of metabotropic glutamate receptors modulates GABAergic transmission to gonadotropin-releasing hormone neurons and alters their firing rate: a possible local feedback circuit
An NMDA receptor/nitric oxide cascade is involved in cerebellar LTD but is not localized to the parallel fiber terminal
Lack of the metabotropic glutamate receptor subtype 7 selectively modulates Theta rhythm and working memory
Modulation of excitatory synaptic transmission by endogenous glutamate acting on presynaptic group II mGluRs in rat substantia nigra compacta
Metabotropic glutamate receptor 8-expressing nerve terminals target subsets of GABAergic neurons in the hippocampus
Tonic facilitation of glutamate release by presynaptic NR2B-containing NMDA receptors is increased in the entorhinal cortex of chronically epileptic rats
Characterization of AMPA receptors targeted by the climbing fiber transmitter mediating presynaptic inhibition of GABAergic transmission at cerebellar interneuron-Purkinje cell synapses
mGluR2 acts through inhibitory Galpha subunits to regulate transmission and long-term plasticity at hippocampal mossy fiber-CA3 synapses
Functional maturation of CA1 synapses involves activity-dependent loss of tonic kainate receptor-mediated inhibition of glutamate release
Astrocyte activation of presynaptic metabotropic glutamate receptors modulates hippocampal inhibitory synaptic transmission
Concomitant deficits in working memory and fear extinction are functionally dissociated from reduced anxiety in metabotropic glutamate receptor 7-deficient mice
The activation of excitatory glutamate receptors evokes a long-lasting increase in the release of GABA from cerebellar stellate cells
Presynaptic kainate receptor activation is a novel mechanism for target cell-specific short-term facilitation at Schaffer collateral synapses
Compartmentalized Ca(2+) channel regulation at divergent mossy-fiber release sites underlies target cell-dependent plasticity
Glycine binding sites of presynaptic NMDA receptors may tonically regulate glutamate release in the rat visual cortex
Group II metabotropic glutamate receptors inhibit glutamate release at thalamocortical synapses in the developing somatosensory cortex
GluR7 is an essential subunit of presynaptic kainate autoreceptors at hippocampal mossy fiber synapses
Differential control of two forms of glutamate release by group III metabotropic glutamate receptors at rat entorhinal synapses
Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial
Antagonism of group III metabotropic glutamate receptors results in impairment of LTD but not LTP in the hippocampal CA1 region, and prevents long-term spatial memory
Developmental switch in the contribution of presynaptic and postsynaptic NMDA receptors to long-term depression
Somatodendritic release of glutamate regulates synaptic inhibition in cerebellar Purkinje cells via autocrine mGluR1 activation
Toward a new role for plasma membrane sodium-dependent glutamate transporters of astrocytes: maintenance of antioxidant defenses beyond extracellular glutamate clearance
Recent progress on the identification of metabotropic glutamate 4 receptor ligands and their potential utility as CNS therapeutics
Activation of group II metabotropic glutamate receptors inhibits the discriminative stimulus effects of alcohol via selective activity within the amygdala
Enhanced sensitivity to attenuation of conditioned reinstatement by the mGluR 2/3 agonist LY379268 and increased functional activity of mGluR 2/3 in rats with a history of ethanol dependence
Proximity of excitatory and inhibitory axon terminals adjacent to pyramidal cell bodies provides a putative basis for nonsynaptic interactions
Selective block of postsynaptic kainate receptors reveals their function at hippocampal mossy fiber synapses
Kainate induces mobilization of synaptic vesicles at the growth cone through the activation of protein kinase A
A systemic transcriptome analysis reveals the regulation of neural stem cell maintenance by an E2F1-miRNA feedback loop
(-)-2-oxa-4-aminobicylco[3.1.0]hexane-4,6-dicarboxylic acid (LY379268) and 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]piperidine (MTEP) similarly attenuate stress-induced reinstatement of cocaine seeking
Pain-related deactivation of medial prefrontal cortical neurons involves mGluR1 and GABA(A) receptors
mGluR1, but not mGluR5, activates feed-forward inhibition in the medial prefrontal cortex to impair decision making
Astrocyte-mediated short-term synaptic depression in the rat hippocampal CA1 area: two modes of decreasing release probability
Neto2 interacts with the scaffolding protein GRIP and regulates synaptic abundance of kainate receptors
State-dependent presynaptic inhibition regulates central pattern generator feedback to descending inputs
Group II metabotropic glutamate receptor stimulation triggers production and release of Alzheimer's amyloid(beta)42 from isolated intact nerve terminals
Presynaptic kainate receptor activation preserves asynchronous GABA release despite the reduction in synchronous release from hippocampal cholecystokinin interneurons
Possibility of a new anti-alzheimer's disease pharmaceutical composition combining memantine and vitamin D
The metabotropic glutamate receptors: potential drug targets for the treatment of anxiety disorders?
Presynaptic ionotropic receptors controlling and modulating the rules for spike timing-dependent plasticity
LPHN3, a presynaptic adhesion-GPCR implicated in ADHD, regulates the strength of neocortical layer 2/3 synaptic input to layer 5
Kainate receptor post-translational modifications differentially regulate association with 4.1N to control activity-dependent receptor endocytosis.
On the Role of Glutamate in Presynaptic Development: Possible Contributions of Presynaptic NMDA Receptors
A novel, extremely fast, feedback inhibition of glutamate release in the crayfish neuromuscular junction
Altered distribution of mGlu2 receptors in β-amyloid-affected brain regions of Alzheimer cases and aged PS2APP mice
Allosteric modulation of metabotropic glutamate receptors: structural insights and therapeutic potential
Effects of the mGlu2/3 agonist LY379268 and the mGlu5 antagonist MTEP on ethanol seeking and reinforcement are differentially altered in rats with a history of ethanol dependence
Metabotropic glutamate receptor 5 activity in the nucleus accumbens is required for the maintenance of ethanol self-administration in a rat genetic model of high alcohol intake
Furthering pharmacological and physiological assessment of the glutamatergic receptors at the Drosophila neuromuscular junction
Radiosynthesis and evaluation of 5-methyl-N-(4-[(11)C]methylpyrimidin-2-yl)-4-(1H-pyrazol-4-yl)thiazol-2-amine ([(11)C]ADX88178) as a novel radioligand for imaging of metabotropic glutamate receptor subtype 4 (mGluR4)
Cell line differences in replication timing of human glutamate receptor genes and other large genes associated with neural disease
Allosteric modulators of NR2B-containing NMDA receptors: molecular mechanisms and therapeutic potential
Activation of group III metabotropic glutamate receptors by endogenous glutamate protects against glutamate-mediated excitotoxicity in the hippocampus in vivo
Glutamate transporter EAAT4 in Purkinje cells controls intersynaptic diffusion of climbing fiber transmitter mediating inhibition of GABA release from interneurons
Pre-synaptic glycine GlyT1 transporter--NMDA receptor interaction: relevance to NMDA autoreceptor activation in the presence of Mg2+ ions
A de novo 8.8-Mb deletion of 21q21.1-q21.3 in an autistic male with a complex rearrangement involving chromosomes 6, 10, and 21
Retrograde plasticity and differential competition of bipolar cell dendrites and axons in the developing retina
Differential expression of metabotropic glutamate and GABA receptors at neocortical glutamatergic and GABAergic axon terminals
Glutamatergic and GABAergic susceptibility loci for heroin and cocaine addiction in subjects of African and European ancestry
Kainate-induced calcium overload of cortical neurons in vitro: Dependence on expression of AMPAR GluA2-subunit and down-regulation by subnanomolar ouabain
The role of glutamate receptors in traumatic brain injury: implications for postsynaptic density in pathophysiology
Zinc potentiates GluK3 glutamate receptor function by stabilizing the ligand binding domain dimer interface
Reduction in Ventral Midbrain NMDA Receptors Reveals Two Opposite Modulatory Roles for Glutamate on Reward
Delayed treatments with pharmacological modulators of pre- and postsynaptic mGlu receptors rescue the hippocampus from kainate-induced neurodegeneration
Differential effects of mGluR7 and mGluR8 activation on pain-related synaptic activity in the amygdala
Role of presynaptic metabotropic glutamate receptors in the induction of long-term synaptic plasticity of vesicular release
ACET is a highly potent and specific kainate receptor antagonist: characterisation and effects on hippocampal mossy fibre function
Behavioral and functional evidence of metabotropic glutamate receptor 2/3 and metabotropic glutamate receptor 5 dysregulation in cocaine-escalated rats: factor in the transition to dependence
Peripheral nerve injury produces a sustained shift in the balance between glutamate release and uptake in the dorsal horn of the spinal cord
The Role of a Novel TRMT1 Gene Mutation and Rare GRM1 Gene Defect in Intellectual Disability in Two Azeri Families
The individual and combined effects of phenmetrazine and mgluR2/3 agonist LY379268 on the motivation to self-administer cocaine
Influence of developmental nicotine exposure on glutamatergic neurotransmission in rhythmically active hypoglossal motoneurons
Therapeutic potential of GABA(B) receptor ligands in drug addiction, anxiety, depression and other CNS disorders
Neuroprotective and Ameliorating Impacts of Omega-3 Against Aspartame-induced Neuronal and Astrocytic Degeneration
Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity
Excessive activation of ionotropic glutamate receptors induces apoptotic hair-cell death independent of afferent and efferent innervation
Pain-related increase of excitatory transmission and decrease of inhibitory transmission in the central nucleus of the amygdala are mediated by mGluR1
Striatin-1 is a B subunit of protein phosphatase PP2A that regulates dendritic arborization and spine development in striatal neurons
The activation of group II metabotropic glutamate receptors protects neonatal rat brains from oxidative stress injury after hypoxia-ischemia
Synthesis and biological activity of argiotoxin 636 and analogues: selective antagonists for ionotropic glutamate receptors
Domain-and species-specific monoclonal antibodies recognize the Von Willebrand Factor-C domain of CCN5
Metabolomics analysis of serum in a rat heroin self-administration model undergoing reinforcement based on 1 H-nuclear magnetic resonance spectra
Targeting metabotropic glutamate receptors in the treatment of epilepsy: rationale and current status
Metabotropic glutamate receptors in median preoptic neurons modulate neuronal excitability and glutamatergic and GABAergic inputs from the subfornical organ
Presynaptic inhibition upon CB1 or mGlu2/3 receptor activation requires ERK/MAPK phosphorylation of Munc18-1
Modulatory effects of activation of metabotropic glutamate receptors on GABAergic circuits in the mouse cortex
Na+,K+-ATPase functionally interacts with the plasma membrane Na+,Ca2+ exchanger to prevent Ca2+ overload and neuronal apoptosis in excitotoxic stress
Lrrc7 mutant mice model developmental emotional dysregulation that can be alleviated by mGluR5 allosteric modulation
Effects of the mGluR2/3 receptor agonist LY379268 on the reinforcing strength of cocaine in rhesus monkeys.
Fluorescence lifetime imaging reveals regulation of presynaptic Ca2+ by glutamate uptake and mGluRs, but not somatic voltage in cortical neurons.
Gq Protein-Coupled Membrane-Initiated Estrogen Signaling Rapidly Excites Corticotropin-Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus in Female Mice
ELFN2 is a postsynaptic cell adhesion molecule with essential roles in controlling group III mGluRs in the brain and neuropsychiatric behavior.
Early Growth Response 1 (Egr-1) Regulates N-Methyl-d-aspartate Receptor (NMDAR)-dependent Transcription of PSD-95 and α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor (AMPAR) Trafficking in Hippocampal Primary Neurons.
Synaptic molecular imaging in spared and deprived columns of mouse barrel cortex with array tomography
Modulatory effects of activation of metabotropic glutamate receptors on GABAergic circuits in the mouse thalamus
Pretreatment with Group II Metabotropic Glutamate Receptor Agonist LY379268 Protects Neonatal Rat Brains from Oxidative Stress in an Experimental Model of Birth Asphyxia
Model-Predicted Balance Between Neural Excitation and Inhibition Was Maintained Despite of Age-Related Decline in Sensory Evoked Local Field Potential in Rat Barrel Cortex
N -Acetylaspartylglutamate (NAAG) Pretreatment Reduces Hypoxic-Ischemic Brain Damage and Oxidative Stress in Neonatal Rats
Sex Differences of Microglia and Synapses in the Hippocampal Dentate Gyrus of Adult Mouse Offspring Exposed to Maternal Immune Activation
Structural dynamics of the GluK3-kainate receptor neurotransmitter binding domains revealed by cryo-EM
Metabotropic Glutamate Receptors in Alzheimer's Disease Synaptic Dysfunction: Therapeutic Opportunities and Hope for the Future.
Unraveling the Nanoscopic Organization and Function of Central Mammalian Presynapses With Super-Resolution Microscopy.
Targeting histone K4 trimethylation for treatment of cognitive and synaptic deficits in mouse models of Alzheimer's disease.
Early-life stress alters affective behaviors in adult mice through persistent activation of CRH-BDNF signaling in the oval bed nucleus of the stria terminalis.
The Dual Role of Glutamatergic Neurotransmission in Alzheimer's Disease: From Pathophysiology to Pharmacotherapy.
Conopeptide-Functionalized Nanoparticles Selectively Antagonize Extrasynaptic N -Methyl-d-aspartate Receptors and Protect Hippocampal Neurons from Excitotoxicity In Vitro
L-Met Activates Arabidopsis GLR Ca2+ Channels Upstream of ROS Production and Regulates Stomatal Movement
High-frequency spinal cord stimulation treatment attenuates the increase in spinal glutamate release and spinal miniature excitatory postsynaptic currents in rats with spared nerve injury-induced neuropathic pain.
Intrathecal Injection of GRIP-siRNA Reduces Postoperative Synaptic Abundance of Kainate Receptor GluK2 Subunits in Rat Dorsal Horns and Pain Hypersensitivity.
The role of G protein-coupled receptors in the early evolution of neurotransmission and the nervous system
The G Protein-Coupled Glutamate Receptors as Novel Molecular Targets in Schizophrenia Treatment-A Narrative Review.
Presynaptic NMDA receptors facilitate short-term plasticity and BDNF release at hippocampal mossy fiber synapses.
Relationships and interactions between ionotropic glutamate receptors and nicotinic receptors in the CNS.
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