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PubMedDate not supplied

Metabotropic glutamate receptors (mGluRs) are involved in early phase of memory formation: possible role of modulation of glutamate release.

Metabotropic glutamate receptors (mGluRs) groups I and II are involved in the cellular processes of long-term potentiation (LTP) and learning and memory formation. I.c.v. injection of the mGluRs agonist 1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) can impair memory formation in some types of learning task. The role of mGluRs in neurotransmitters release and production of second messengers has been suggested. The aim of the present study was to determine the effect of i.c.v. administration of the new potent mGluRs agonist ABHxD-I and compare its effect with that of ACPD. We studied the effect of both agonists on acquisition and memory for a one-trial passive avoidance learning task in day-old chicks and on the training related glutamate (Glu) release. ACPD or ABHxD-I (50 nmole per chick, i.c.v. injection) were administered at different times before or after training and chicks were tested at various times after training. Chicks injected with ABHxD-I 30 min before training showed amnesia when tested 30 min or 3h after training. The amnestic effect of ACPD was significant only 30 min after training. Glu release evoked by 70 mM KCl was measured in slices prepared from the IMHV of chick brain isolated from animals injected with either ACPD or ABHxD-I 30 min before training and tested 30 min after training. Glu concentration was measured using HPLC. Both ACPD and ABHxD-I significantly increased Glu release in slices isolated from untrained chicks (30 and 48% compare to control, respectively, P<0.05). Training itself increased Glu release (41% compared to control, P<0.01) and no additional effect of either ACPD or ABHxD-I was observed. These results suggest that mGluRs groups I and II are involved in the early stages of memory formation and that application of either of the studied mGluRs agonists may interfere with that process. The amnestic effect of ABHxD-I seems to be stronger and longer lasting. Although the mechanism of this effect still remains unclear, our results suggest that disregulation of Glu release by mGluR agonists may participate in this process.

Animals↗

PubMed1998

Calcium influx via ionotropic glutamate receptors causes long lasting inhibition of metabotropic glutamate receptor-coupled phosphoinositide hydrolysis.

Functional interaction between ionotropic and metabotropic glutamate receptors (iGluR and mGluR respectively) was studied in cerebellar granule cell cultures using quisqualate (QA), the most potent agonist of phosphoinositide hydrolysis coupled mGluR, and N-methyl-D-aspartate (NMDA) or kainate (KA) that activate different classes of iGluR. Two h exposure to NMDA or KA resulted in a marked reduction (about 75%) of QA-evoked PI hydrolysis. The efficacy of the two agonists was about the same, but the potencies were different (IC50 for NMDA about 35 microM and for KA about 70 microM). NMDA-induced depression of QA-stimulated PI hydrolysis was relatively long lasting but reversible. Recovery required protein synthesis. In nominally Ca2+-free medium both NMDA and KA failed to attenuate QA-stimulated PI hydrolysis. The effect of NMDA was prevented by the NMDA receptor antagonist MK801, but not by the wide spectrum protein kinase inhibitor staurosporin nor by the nitric oxide synthase inhibitor N omega-nitro-L-arginine. Cycloheximide and concanavalin A were also ineffective. The effect of KA was prevented by the selective non-NMDA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX). Voltage sensitive Ca2+ channel antagonists together with MK801 did not counteract the inhibition by KA of the QA response. Both NMDA and KA attenuated PI hydrolysis evoked by the muscarinic receptor agonist carbachol (about 30%), indicating that the activation of iGluRs exerts a relatively general inhibitory effect on the function of different PLC-coupled metabotropic receptors. Consistent with this observation is that treatments either with KA and NMDA induced an inhibition (about 30%) of NaF-stimulated PI hydrolysis which occurs through the direct activation of G proteins. Our observations show that ionotropic glutamate receptor stimulation induces a long lasting suppression of QA-evoked PI breakdown through a Ca2+ dependent mechanism which seems to involve receptor coupled transduction systems downstream from mGluR. Such a Ca2+-dependent cross-talk involving ionotropic and metabotropic receptors may play a role in certain events of synaptic plasticity.

Animals↗

PubMed1998

Synthesis and metabotropic glutamate receptor activity of a 2-aminobicyclo[3.2.0]heptane-2,5-dicarboxylic acid, a molecule possessing an extended glutamate conformation.

A photochemical approach to the synthesis of the aminobicycloheptane 6a is reported. This compound assumes an extended glutamate conformation, and for this reason was created to further probe the structural features relevant to achieving selectivity for the subtypes of the metabotropic glutamate family of receptors.

Animals↗

PubMed2003

Synthesis and in vitro pharmacology at AMPA and kainate preferring glutamate receptors of 4-heteroarylmethylidene glutamate analogues.

2-Amino-3-[3-hydroxy-5-(2-thiazolyl)-4-isoxazolyl]propionic acid (1) is a potent AMPA receptor agonist with moderate affinity for native kainic acid (KA) receptors, whereas (S)-E-4-(2,2-dimethylpropylidene)glutamic acid (3) show high affinity for the GluR5 subtype of KA receptors and much lower affinity for the GluR2 subtype of AMPA receptors. As an attempt to develop new pharmacological tools for studies of GluR5 receptors, (S)-E-4-(2-thiazolylmethylene)glutamic acid (4a) was designed as a structural hybrid between 1 and 3. 4a was shown to be a potent GluR5 agonist and a high affinity ligand and to indiscriminately bind to the AMPA receptor subtypes GluR1-4 with lower affinities. Compounds 4b-h, in which the 2-thiazolyl substituent of 4a was replaced by other heterocyclic rings, which have previously been incorporated as 5-substituents in AMPA analogues, as exemplified by 1 were also synthesized. Compounds 4b-h were either inactive (4e,f) or weaker than 4a as affinity ligands for GluR1-4 and GluR5 with relative potencies comparable with those of the corresponding AMPA analogues as AMPA receptor agonists. Compounds 4a-h may be useful tools for the progressing pharmacophore mapping of the GluR5 agonist binding site.

Animals↗

PubMed2005

On the binding determinants of the glutamate agonist with the glutamate receptor ligand binding domain.

Ionotropic glutamate receptors (GluRs) are ligand-gated membrane channel proteins found in the central neural system that mediate a fast excitatory response of neurons. In this paper, we report theoretical analysis of the ligand-protein interactions in the binding pocket of the S1S2 (ligand binding) domain of the GluR2 receptor in the closed conformation. By utilizing several theoretical methods ranging from continuum electrostatics to all-atom molecular dynamics simulations and quantum chemical calculations, we were able to characterize in detail glutamate agonist binding to the wild-type and E705D mutant proteins. A theoretical model of the protein-ligand interactions is validated via direct comparison of theoretical and Fourier transform infrared spectroscopy (FTIR) measured frequency shifts of the ligand's carboxylate group vibrations [Jayaraman et al. (2000) Biochemistry 39, 8693-8697; Cheng et al. (2002) Biochemistry 41, 1602-1608]. A detailed picture of the interactions in the binding site is inferred by analyzing contributions to vibrational frequencies produced by protein residues forming the ligand-binding pocket. The role of mobility and hydrogen-bonding network of water in the ligand-binding pocket and the contribution of protein residues exposed in the binding pocket to the binding and selectivity of the ligand are discussed. It is demonstrated that the molecular surface of the protein in the ligand-free state has mainly positive electrostatic potential attractive to the negatively charged ligand, and the potential produced by the protein in the ligand-binding pocket in the closed state is complementary to the distribution of the electrostatic potential produced by the ligand itself. Such charge complementarity ensures specificity to the unique charge distribution of the ligand.

Algorithms↗

PubMed1998

Glutamate-induced Co2+ uptake in rat auditory brainstem neurons reveals developmental changes in Ca2+ permeability of glutamate receptors.

Ca2+ influx through glutamate receptors (GluRs) is thought to play a crucial part in developmental processes and neuronal plasticity. Here we have examined the spatiotemporal distribution of Ca2+-permeable GluRs in auditory brainstem neurons of the rat from birth to adulthood, using the cobalt-staining technique of Pruss and collaborators. In slices of young adult rats, 1 mM glutamate evoked intense cobalt uptake in subsets of neurons in the ventral cochlear nuclei, the medial nucleus of the trapezoid body, the lateral and the medial superior olive, and the lateral lemniscal nuclei. Neurones in the central nucleus of the inferior colliculus, and thalamic auditory nuclei appear to express few, if any, Ca2+-permeable GluRs. Thus, in adults, Ca2+-permeable GluRs are present in neurons of almost all main relay stations of the auditory brainstem. During development, cobalt-stained cells first appeared at about hearing onset (at postnatal day 12 [P12]). At P16, staining levels were highest and the pattern of distribution was already adult-like. The staining intensity slightly declined during the fourth postnatal week. In contrast, Ca2+-permeable receptors were detected in the external cortex of the inferior colliculus as early as P4. Our results show that auditory neurons, characterized by a high temporal precision in neuronal activity, display Ca2+-permeable GluRs. Because Ca2+ permeability appears at about the onset of hearing and is highest during the following 2 weeks, Ca2+ influx through GluRs is likely to be implicated in remodelling processes occurring during this ontogenetic period.

Animals↗

PubMed2000

Circadian variations in plasma and erythrocyte glutamate concentrations in adult men consuming a diet with and without added monosodium glutamate.

This study evaluated the effect of monosodium glutamate (MSG) ingestion as a component of the diet on the 24-h variations in plasma and whole-blood glutamate (GLU) concentrations in healthy adult men. In the first arm of the study, subjects were given test meals without added MSG for 3 d. Protein and energy intakes of the subjects were 1.5 g and 40 kcal/(kg body weight.d), respectively. On d 3, blood samples were collected over the 24-h period. One week later, the same protocol was repeated, except that 100 mg/(kg body weight.d) MSG was added to the meals (15, 40 and 45 mg/kg body weight to breakfast, lunch and dinner, respectively). Both plasma and whole-blood samples were analyzed for free amino acids. Unlike large neutral amino acids, which experienced high peak plasma concentrations at 2100-2300 h, the circadian variations in plasma GLU concentrations were small, varying between 33 and 48 micromol/L on days in which no MSG was fed, and between 32 and 53 micromol/L on days in which MSG was added to the meals. In both trials, plasma GLU concentration increased (P < 0.01) after lunch and dinner, and decreased early in the morning (P < 0.05). Calculated erythrocyte GLU concentrations varied between 500 and 640 micromol/L, with or without MSG addition to the meals. The rather low plasma GLU concentrations over the 24-h period, despite high dietary intake of MSG, indicate that dietary MSG is metabolized very rapidly.

Adult↗

PubMed2005

Localization of NAD-isocitrate dehydrogenase and glutamate dehydrogenase in rice roots: candidates for providing carbon skeletons to NADH-glutamate synthase.

In rice roots, transient and cell-type-specific accumulation of both mRNA and protein for NADH-dependent glutamate synthase (NADH-GOGAT) occurs after the supply of NH(4) (+) ions. In order to better understand the origin of 2-oxoglutarate for this reaction, we focused on mitochondrial NAD-dependent isocitrate dehydrogenase (IDH) and glutamate dehydrogenase (GDH) in rice roots. Six rice cDNAs encoding a single catalytic (OsIDHa) and two regulatory (OsIDHc;1, OsIDHc;2) IDH subunits and three GDH proteins (OsGDH1-3) were isolated. These genes, except OsGDH3, were expressed in the roots. Real-time PCR analysis showed that OsIDHa and OsIDHc;1 transcripts, but not OsGDH1 and OsGDH2 transcripts, accumulated in a similar manner to NADH-GOGAT mRNA along the crown roots after the supply of different forms of inorganic nitrogen. Furthermore, immunolocalization studies revealed the NH(4) (+) induction of IDHa protein in two cell layers of the root surface, i.e. epidermis and exodermis, where NADH-GOGAT also accumulated. The possible relationship between NADH-GOGAT, IDH and GDH is discussed.

Amino Acid Sequence↗

PubMed2001

Glutamate synthase of Corynebacterium glutamicum is not essential for glutamate synthesis and is regulated by the nitrogen status.

The Corynebacterium glutamicum gltB and gltD genes, encoding the large (alpha) and small (beta) subunit of glutamate synthase (GOGAT), were investigated in this study. Using RT-PCR, a common transcript of gltB and gltD was shown. Reporter gene assays and Northern hybridization experiments revealed that transcription of this operon depends on nitrogen starvation. The expression of gltBD is under control of the global repressor protein AmtR as demonstrated by gel shift experiments and analysis of gltB transcription in an amtR deletion strain. In contrast to other bacteria, in C. glutamicum GOGAT plays no pivotal role; e.g. gltB and gltD inactivation did not result in growth defects when cells were grown in standard minimal medium and only a slight increase in the doubling time of the corresponding mutant strains was observed in the presence of limiting amounts of ammonia or urea. Additionally, mutant analyses revealed that GOGAT has no essential function in glutamate production by C. glutamicum.

Bacterial Proteins↗

PubMed2001

Identification of essential residues involved in the glutamate binding pocket of the group II metabotropic glutamate receptor.

Metabotropic glutamate (mGlu) receptors are a family of G-protein-coupled receptors that play central roles as modulators of both glutamatergic and other major neurotransmitter systems in CNS. Using molecular modeling, site-directed mutagenesis, [(3)H]LY354740 binding, [(35)S]GTPgammaS binding, and activation of GIRK current, we have been able to identify residues crucial for the binding of LY354740 and glutamate to rat mGlu2 receptors. Several of the crucial residues located in the binding site (Arg-57, Tyr-144, Tyr-216, Asp-295) have not been identified previously. We propose that the gamma-carboxyl group of LY354740 forms H-bonds to Arg-57, whereas the alpha-carboxyl group forms an H-bond with the hydroxyl group of Ser-145. The alpha-amino group of LY354740 forms H-bonds to Asp-295 and to the side-chain hydroxyl group of Thr-168. In addition, Tyr-144 may establish a hydrophobic (C-H/pi)-interaction with the bicyclo-hexane ring of LY354740. Furthermore, the mutation of residues Ser-148 and Arg-183, which are too remote for a direct interaction, affected the ligand affinity dramatically. These results suggest that Ser-148 and Arg-183 may be important for the 3D structure and/or are involved in closure of the domain. Finally, Asp-146, which is also remote from the binding site, was shown to be involved in the differential binding affinity of [(3)H]LY354740 for mGlu2 versus mGlu3 receptors. All the mGlu receptors except mGlu2 are activated by Ca(2+) and have serine instead of aspartic acid at this position, which suggests a critical role of this aspartic acid residue in the binding properties of this unique receptor.

Amino Acids↗

PubMed2025

Mutant gltS alleles enable a Vibrio fischeri D-glutamate auxotroph to grow with lower requirements for exogenous D-glutamate.

D-glu is a key component of peptidoglycan (PG) and is essential for growth in most bacteria. To assess constraints on PG evolution and bacterial requirements for D-glu, we sought to artificially evolve PG biosynthesis, leading to either replacement of D-glu in the PG peptide or alternative pathways to D-glu incorporation. We previously found that suppression of D-glu auxotrophy in a murI racD mutant of Vibrio fischeri grown on lysogeny broth salts (LBS) medium was rare but could be accomplished by mutation of bsrF, with restoration of wild-type PG structure. Here, we selected nine additional prototrophic suppressors of the same murI racD mutant from 1010 colony-forming units (CFU) plated on LBS supplemented with ~2.7 mM D-gln. Each suppressor had a mutation in gltS, which encodes a putative sodium:glutamate symporter. Increased copy numbers of mutant gltS alleles enabled growth on unsupplemented LBS and resulted in PG containing D-glu. Examination of media components suggests that D-gln supplementation had inadvertently added ~14 μM D-glu, and that LBS itself contains ~1.4 μM D-glu. The mutations in gltS enabled growth with similarly low D-glu concentrations, but also increased sensitivity to homocysteic acid, suggesting more promiscuous transport. Surprisingly, we discovered that expression of mutant gltS in the auxotroph leads to incorporation of lysine into PG, in addition to canonical D-glu. When seawater is supplemented with D-glu, this V. fischeri mutant still colonized Euprymna scolopes and triggered PG-induced morphogenesis. Our results shed light on glutamate transport, highlight trade-offs in GltS structure and function, and reveal an unusual PG modification.IMPORTANCED-glu is an important building block in the peptidoglycan (PG) component of the bacterial cell wall, and its endogenous production is considered essential in most bacteria, even when grown in complex media. In Vibrio fischeri, in trans expression of mutant GltS symporters allows D-glu auxotrophic strains to grow on lysogeny broth salts (LBS) medium without exogenous D-glu, although there is a fitness trade-off of increased sensitivity to homocysteic acid. Our finding that LBS contains sufficient D-glu to support robust growth highlights the undervalued importance of D-amino acid transport and the ubiquity of D-amino acids. Moreover, the discovery of D-lysine in the PG peptide is an unusual PG modification that warrants further study.

Aliivibrio fischeri↗

PubMedDate not supplied

Glutamic acid and glutamic acid diethylester in tinnitus treatment.

Numerous recent findings indicate that in mammals glutamic acid (Glu) functions as the primary and secondary afferent cochlear transmitter, or at least as an agonist of the main transmitter. Glutamic acid diethylester (GDEE) is one of the known antagonists of Glu. A long term suppression of certain forms of tinnitus was observed dependent on the sequence, amount and perfusion rate upon i.v. application of Glu and GDEE. Consecutive controls with tinnitus detecting as well as blind studies helped to objectify the subjective sensations of the patients.

Glutamates↗

PubMed1998

[Effects of glutamate, glutamate receptor in limbic system and hypothalamus on hypothalamus-pituitary-adrenal axis after rats MCAO].

OBJECTIVE: To investigate the features of activity changes of glutamate(Glu), glutamate receptors(GluR) in hippocampus and hypothalamus during rats middle cerebral artery occlusion (MCAO) or reperfusion. METHODS: Using radio-legend binding assay of receptor (RBA), high-performance liquid chromatography (HPLC) and hybridization in situ and radioimmunometric assay, (RIA), we determined the dynamic changes of Glu content, GluR capacity and it's Kd in cell membrane from the hippocampus of the ischemic brain and the hypothalamus CRHmRNA expression levels in every brain areas and ACTH concentrations in plasma at different time after middle cerebral artery occlusion(MCAO) or reperfusion. RESULTS: Glu content rapidly increased in the hippocampus and the hypothalamus at 15 minutes after MCAO, and reached the peak values at I1 h, and rapidly decreased to the basic-line level after reperfusion. Glu content IR24 h to IR48 h, was elevated again moderately, and declined slowly 48 hours after reperfusion. The GluR was down-regulated and the affinity enhanced in during the ischemic period. During the reperfusion period, the GluR was typically up-regulated. The CRHmRNA expressive levels were markedly enhanced in the tempol cortex, the hippocampus and the hypothalamus at I1 h, and kept to IR96 h, the ACTH concentration in the plasma increased relatively. In the peak time of reperfusion, the Glu content of hypothalamus was positively corrected with CRHmRNA expressive positive cell amounts of the hypothalamus. CONCLUSION: CRH may aggravate ischemic neuronal damage, and Glu participates in the pathogenesis of HPA axis be excited strongly and may be an important impel factor for ACI specially condition.

Animals↗

PubMed2001

Roles of glutamate receptor delta 2 subunit (GluRdelta 2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber synapse elimination during postnatal cerebellar development.

Climbing fiber (CF) synapse formation onto cerebellar Purkinje cells (PCs) is critically dependent on the synaptogenesis from parallel fibers (PFs), the other input to PCs. Previous studies revealed that deletion of the glutamate receptor delta2 subunit (GluRdelta2) gene results in persistent multiple CF innervation of PCs with impaired PF synaptogenesis, whereas mutation of the metabotropic glutamate receptor subtype 1 (mGluR1) gene causes multiple CF innervation with normal PF synaptogenesis. We demonstrate that atypical CF-mediated EPSCs (CF-EPSCs) with slow rise times and small amplitudes coexisted with typical CF-EPSCs with fast rise times and large amplitudes in PCs from GluRdelta2 mutant cerebellar slices. CF-EPSCs in mGluR1 mutant and wild-type PCs had fast rise times. Atypical slow CF responses of GluRdelta2 mutant PCs were associated with voltage-dependent Ca(2+) signals that were confined to PC distal dendrites. In the wild-type and mGluR1 mutant PCs, CF-induced Ca(2+) signals involved both proximal and distal dendrites. Morphologically, CFs of GluRdelta2 mutant mice extended to the superficial regions of the molecular layer, whereas those of wild-type and mGluR1 mutant mice did not innervate the superficial one-fifth of the molecular layer. It is therefore likely that surplus CFs of GluRdelta2 mutant mice form ectopic synapses onto distal dendrites, whereas those of wild-type and mGluR1 mutant mice innervate proximal dendrites. These findings suggest that GluRdelta2 is required for consolidating PF synapses and restricting CF synapses to the proximal dendrites, whereas the mGluR1-signaling pathway does not affect PF synaptogenesis but is involved in eliminating surplus CF synapses at the proximal dendrites.

Aging↗

PubMed2004

Inhibitory effects of Cimicifuga heracleifolia extract on glutamate formation and glutamate dehydrogenase activity in cultured islets.

Hyperinsulinism-hyperammonemia syndrome is due either to hyperactivity of GDH or impaired inhibition of GDH by GTP. We have investigated the effect of Cimicifuga heracleifolia extract on the activities of glutamate dehydrogenase (GDH) in cultured rat islets. When the extract was present in the culture medium for 24 h prior to cell harvest, the Vmax of GDH was decreased by 45% with no significant change in Km. In addition, the concentration of alpha-ketoglutarate increased by approximately 39%, and glutamate decreased by 48%. Perfusion of islets with C. heracleifolia extract reduced insulin release by up to 47%. Although the relation between GDH activity and insulin release remains to be clarified, our results suggest that C. heracleifolia extract regulates insulin release by altering GDH activity in primary cultured islets and that this natural compound may be used to modulate GDH activity in patients with hyperinsulinism-hyperammonemia syndrome.

Animals↗

PubMed1995

A role for glutamate decarboxylase during tomato ripening: the characterisation of a cDNA encoding a putative glutamate decarboxylase with a calmodulin-binding site.

A tomato fruit cDNA library was differentially screened to identify mRNAs present at higher levels in fruit of the tomato ripening mutant rin (ripening inhibitor). Complete sequencing of a unique clone ERT D1 revealed an open reading frame with homology to several glutamate decarboxylases. The deduced polypeptide sequence has 80% overall amino acid sequence similarity to a Petunia hybrida glutamate decarboxylase (petGAD) which carries a calmodulin-binding site at its carboxyl terminus and ERT D1 appears to have a similar domain. ERT D1 mRNA levels peaked at the first visible sign of fruit colour change during normal tomato ripening and then declined, whereas in fruit of the ripening impaired mutant, rin, accumulation of this mRNA continued until at least 14 days after the onset of ripening. This mRNA was present at much lower levels in other tissues, such as leaves, roots and stem, and was not increased by wounding. Possible roles for GAD, and its product gamma-aminobutyric acid (GABA) in fruit, are discussed.

Amino Acid Sequence↗

PubMed2001

Metabotropic glutamate receptors modify ionotropic glutamate responses in neocortical pyramidal cells and interneurons.

In neocortex glutamate activates ionotropic and metabotropic receptors (mGluRs). Whole-cell current-clamp recordings in the in vitro rat auditory cortex at 32 degrees C were used to explore the role that mGluRs have in regulation of AMPA/kainate, NMDA, and GABA receptor-mediated synaptic transmission. Our findings are: (a) The fast EPSP (AMPA/kainate), slow EPSP (NMDA), and IPSPs (GABAA, GABAB), elicited in pyramidal neurons are reduced in the presence of (1S,3R)-ACPD (mGluR agonist) with greatest effect on the slow IPSP>fast IPSP>>fast EPSP. The effect is likely the result of ACPD acting at presynaptic mGluRs because the probability of release of glutamate and GABA is reduced in the presence of ACPD, intracellular infusion of a G protein antagonist (GDPPS) did not block the effect of ACPD, nor were iontophoretic kainic acid or NMDA-induced depolarizations reduced by ACPD. (b) The slow EPSP is enhanced following washout of ACPD and enhancement is not due to disinhibition because it is present in the absence of IPSPs, but if IPSPs are present, its magnitude can be influenced. Iontophoretic NMDA responses are enhanced in the presence of ACPD, an effect blocked by GDPbetaS and heparin (intracellular inositol 1,4,5-trisphosphate receptor antagonist). Taken together, this evidence suggests that enhancement is a result of group I postsynaptic mGluR activation. (c) In fast-spiking cells ACPD reduces the EPSP (AMPA/kainate and NMDA-mediated). This action is likely presynaptic because it persists when GDPbetaS is in the cells. (d) The rate of spike discharge recorded from fast-spiking cells is accelerated in ACPD but does not change in the presence of GDPbetaS, suggesting a postsynaptic effect. Our data indicate that mGluRs can influence neocortical synaptic transmission in complex ways by acting presynaptically and postsynaptically.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1998

Differential localisation of the metabotropic glutamate receptor mGluR1a and the ionotropic glutamate receptor GluR2/3 in neurons of the human cerebral cortex.

Specimens of human cerebral cortex were obtained during neurosurgical operations and studied by immunocytochemistry and electron microscopy, using antibodies to the metabotropic glutamate receptor subunit mGluR1a and the ionotropic glutamate receptor GluR2/3. A small number of non-pyramidal neuronal cell bodies were labelled for mGluR1a. Double immunolabelling with mGluR1a and GluR2/3 showed that most pyramidal cell bodies were labelled for GluR2/3 but not for mGluR1a. Despite the non-colocalisation of these two receptor subtypes in cell bodies, however, many dendrites and dendritic spines were double-labelled for mGluR1a and GluR2/3 at electron microscopy. As there is evidence that most neurons positive for GluR2/3 are pyramidal cells, this suggests that mGluR1a is present in dendrites of pyramidal neurons, despite absent or low levels of immunoreactivity in their cell bodies.

Adolescent↗