Cyclosporine-A treatment prevents apoptosis in rat lumbar ganglion cells

We evaluated the expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 in lumbar ganglion cells of rats by immunohistochemistry under normal conditions and after 7, 14 and 21 days of cyclosporine-A treatment (7 and 15 mg/kg/daily). In normal rats, Bax was weakly expressed in all types of neurons, whereas satellite cells showed moderate immunostaining. Bcl-2 expression was weak in type A neurons and weak or moderate in type B and C neurons and also into satellite cells. In cyclosporine-A-treated rats, we found changes in Bax staining of neurons: type A neurons and type B neurons were weakly stained, whereas type C neurons were moderately stained. Bax expression in satellite cells was moderate after 7 days of treatment and increased strongly after 14 and 21 days of treatment. Bcl-2 expression increased significantly in neurons after 14 and even more after 21 days of treatment with 7 mg/kg cyclosporine-A, mainly in type B and C neurons. With 15 mg/kg cyclosporine-A, Bcl-2 increased moderately in type A and B neurons and strongly in type C neurons only after 7 days. After 14 and 21 days, Bcl-2 expression was moderate in type A neurons whereas it was strong or even very strong in type B and C neurons. Satellite cells showed a moderate increase in Bcl-2 after 7 and 14 days of treatment whereas after 21 days, expression was strong. We conclude that (1) in normal conditions, Bax and Bcl-2 were differently expressed in neurons and satellite cells; (2) cyclosporine-A treatment rapidly enhanced Bax expression in satellite cells only, whereas Bcl-2 expression increased moderately in type A neurons and was strongly expressed in type B and C neurons; (3) cyclosporine-A has a protective role in neurons but not in satellite cells; and (4) the neuroprotective role of cyclosporine-A is dose dependent. Furthermore, the strong expression of Bax in satellite cells can explain the temporary nature of the neurotoxic effect commonly observed after cyclosporine-A administration.     

Cellular localization of metabotropic glutamate receptors in cortical tubers and subependymal giant cell tumors of tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder associated with cortical malformations (cortical tubers) and the development of glial tumors (subependymal giant-cell tumors, SGCTs). Expression of metabotropic glutamate receptor (mGluR) subtypes is developmentally regulated and several studies suggest an involvement of mGluR-mediated glutamate signaling in the regulation of proliferation and survival of neural stem-progenitor cells, as well as in the control of tumor growth. In the present study, we have investigated the expression and cell-specific distribution of group I (mGluR1, mGluR5), group II (mGluR2/3) and group III (mGluR4 and mGluR8) mGluR subtypes in human TSC specimens of both cortical tubers and SGCTs, using immunocytochemistry. Strong group I mGluR immunoreactivity (IR) was observed in the large majority of TSC specimens in dysplastic neurons and in giant cells within cortical tubers, as well as in tumor cells within SGCTs. In particular mGluR5 appeared to be most frequently expressed, whereas mGluR1alpha was detected in a subpopulation of neurons and giant cells. Cells expressing mGluR1alpha and mGluR5, demonstrate IR for phospho-S6 ribosomal protein (PS6), which is a marker of the mammalian target of rapamycin (mTOR) pathway activation. Group II and particularly group III mGluR IR was less frequently observed than group I mGluRs in dysplastic neurons and giant cells of tubers and tumor cells of SGCTs. Reactive astrocytes were mainly stained with mGluR5 and mGluR2/3. These findings expand our knowledge concerning the cellular phenotype in cortical tubers and in SGCTs and highlight the role of group I mGluRs as important mediators of glutamate signaling in TSC brain lesions. Individual mGluR subtypes may represent potential pharmacological targets for the treatment of the neurological manifestations associated with TSC brain lesions.     

Immunohistochemical localization of group I and II metabotropic glutamate receptors in control and amyotrophic lateral sclerosis human spinal cord: upregulation in reactive astrocytes.

Excitotoxicity, which is mediated by the excessive activation of glutamate receptors, has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). There is substantial information about the distribution and function of ionotropic glutamate receptors in the spinal cord, although the role of metabotropic glutamate receptors (mGluRs) is poorly understood in this region of the brain, particularly under pathological conditions. We used immunocytochemistry to study the general distribution of group I and group II mGluR immunoreactivity in the human spinal cord, as well as the cell-specific expression of these receptors. We also investigated whether mGluR expression was altered in the spinal cord of patients with sporadic and familial ALS. Immunocytochemical analysis of control human spinal cord demonstrated that mGluR1alpha and mGluR5 (group I mGluRs) were highly represented in neuronal cells throughout the spinal cord. mGluR1alpha showed the highest relative level of expression in ventral horn neurons (laminae VIII and IX), whereas intense mGluR5 immunoreactivity was observed within the dorsal horn (superficial laminae I and II). Group II mGluRs (mGluR2/3) immunoreactivity was mainly concentrated in the inner part of the lamina II. With respect to specific neuronal populations, mGluR2/3 and mGluR5 appeared to be most frequently expressed in calbindin-containing and calretinin-containing cells, respectively. In control spinal cord only sparse astrocytes showed a weak to moderate mGluR immunoreactivity. Regional differences in immunoreactivity were apparent in ALS compared to control. In particular, mGluR expression was increased in reactive glial cells in both gray (ventral horn) and white matter of ALS spinal cord. Upregulation of mGluRs in reactive astrocytes may represent a critical mechanism for modulation of glial function and changes in glial-neuronal communication in the course of neurodegenerative diseases.     

Upregulation of metabotropic glutamate receptor 8 mRNA expression in the rat forebrain after repeated amphetamine administration

Metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors and are densely expressed in the forebrain of adult rats. Accumulative evidence suggests a critical role of mGluRs in the regulation of normal physiological activity of neurons and pathogenesis of mental illnesses such as schizophrenia, depression, and substance addiction. In this study, we investigated alterations in mGluR8 subtype mRNA expression in the rat forebrain in response to repeated intraperitoneal administration of amphetamine (twice daily for 12 days, 5mg/kg per injection) using quantitative in situ hybridization. We found that mGluR8 mRNA levels were profoundly increased in the dorsal (caudate putamen) and ventral (nucleus accumbens) striatum 1 day after the discontinuation of amphetamine treatments. Such increases were sustained up to 21 days of withdrawal. Increases in mGluR8 mRNAs were also found in the cerebral cortex, including the cingulate and sensory cortex but not the piriform cortex, at 1 and 21 days. These data demonstrate a positive response of mGluR8 in mRNA abundance in most forebrain regions to repeated stimulant exposure.     

Group I and II metabotropic glutamate receptor expression in cultured rat spinal cord astrocytes

We have examined the development of expression of group I and II metabotropic glutamate receptors (mGluRs) in pure rat spinal cord astrocyte cultures, using immunocytological and calcium imaging techniques. mGluR1alpha and mGluR2/3 antibodies were found to label roughly 10% of the total astrocyte population at all time points examined, whereas mGluR5 was poorly expressed in our culture system. Results from intracellular Ca2+ imaging experiments, measured using fura-2 ratio imaging, suggest that 20% of these cultured astrocytes express functional group I mGluRs (mGluR1 and/or 5). Our results contrast with previously published work in cultured cortical astrocytes where mGluR5 and not mGluR1 is expressed, suggesting that cultured astrocytes from different parts of the CNS exhibit different patterns of mGluR expression.     

The role of metabotropic glutamate receptors in regulation of striatal proenkephalin expression: implications for the therapy of Parkinson's disease

Overactivity of the striatopallidal pathway, associated with an enhancement of enkephalin expression, has been suggested to contribute to the development of parkinsonian symptoms. The aim of the present study was to examine whether the blockade of group I metabotropic glutamate receptors: subtypes 1 and 5 (mGluR1/5), or stimulation of group II: subtypes 2 and 3 (mGluR2/3) may normalize enkephalin expression in the striatopallidal pathway in an animal model of parkinsonism. The proenkephalin mRNA level measured by in situ hybridization in the striatum was increased by pretreatments with haloperidol (1.5 mg/kg s.c., three times, 3 h apart). Triple (3 h apart), bilateral, intrastriatal administration of selective antagonists of mGluR1: (S)-(+)-alpha-amino-4-carboxy-2-methylbenzeneacetic acid (3 x 5 microg/0.5 microl) or 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate (3 x 2.5 microg/0.5 microl), reversed the haloperidol-induced increases in proenkephalin mRNA levels in the rostral and central regions of the striatum. Similarly, repeated (6 times, 1.5 h apart), systemic injections of an antagonist of mGluR5, 2-methyl-6-(phenylethynyl)pyridine (6 x 10 mg/kg i.p.) counteracted an increase in the striatal proenkephalin mRNA expression elicited by haloperidol. None of the abovementioned antagonists of mGluR1 and mGluR5 per se influenced the proenkephalin expression. Differential effects were induced by agonists of the group II mGluRs, viz. (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine administered intraventricularly (3 times at 0.1-0.2 microg/4 microl, 3 h apart) increased both the normal and haloperidol-increased proenkephalin mRNA level, whereas (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate injected intrastriatally (3 times at 15 microg/0.5 microl, 3 h apart) was ineffective. The present study indicates that the blockade of striatal glutamate receptors belonging to the group I (mGluR1 and mGluR5) but not stimulation of the group II mGluRs may normalize the function of the striatopallidal pathway in an animal model of parkinsonism, which may be important for future antiparkinsonian therapy in humans.     

Distribution of metabotropic glutamate receptor mGluR3 in the mouse CNS: differential location relative to pre- and postsynaptic sites

The metabotropic glutamate receptors (mGluRs) have distinct distribution patterns in the CNS but subtypes within group I or group III mGluRs share similar ultrastructural localization relative to neurotransmitter release sites: group I mGluRs are concentrated in an annulus surrounding the edge of the postsynaptic density, whereas group III mGluRs are concentrated in the presynaptic active zone. One of the group II subtypes, mGluR2, is expressed in both pre- and postsynaptic elements, having no close association with synapses. In order to determine if such a distribution is common to another group II subtype, mGluR3, an antibody was raised against a carboxy-terminus of mGluR3 and used for light and electron microscopic immunohistochemistry in the mouse CNS. The antibody reacted strongly with mGluR3, but it also reacted, though only weakly, with mGluR2. Therefore, to examine mGluR3-selective distribution, we used mGluR2-deficient mice as well as wild-type mice.Strong immunoreactivity for mGluR3 was found in the cerebral cortex, striatum, dentate gyrus of the hippocampus, olfactory tubercle, lateral septal nucleus, lateral and basolateral amygdaloid nuclei, and nucleus of the lateral olfactory tract. Pre-embedding immunoperoxidase and immunogold methods revealed mGluR3 labeling in both presynaptic and postsynaptic elements, and also in glial profiles. Double labeling revealed that the vast majority of mGluR3 in presynaptic elements is not closely associated with glutamate and GABA release sites in the striatum and thalamus, respectively. However, in the spines of the dentate granule cells, the highest receptor density was found in perisynaptic sites (20% of immunogold particles within 60 nm from the edge of postsynaptic membrane specialization) followed by a decreasing receptor density away from the synapses (to approximately 5% of particles per 60 nm). Furthermore, 19% of immunogold particles were located in asymmetrical postsynaptic specialization, indicating an association of mGluR3 to glutamatergic synapses.The present results indicate that the localization of mGluR3 is rather similar to that of group I mGluRs in the postsynaptic elements, suggesting a unique functional role of mGluR3 in glutamatergic neurotransmission in the CNS.     

Group I metabotropic glutamate receptors are differentially expressed by two populations of olfactory bulb granule cells

In the main olfactory bulb, several populations of granule cells (GCs) can be distinguished based on the soma location either superficially, interspersed with mitral cells within the mitral cell layer (MCL), or deeper, within the GC layer (GCL). Little is known about the physiological properties of superficial GCs (sGCs) versus deep GCs (dGCs). Here, we used patch-clamp recording methods to explore the role of Group I metabotropic glutamate receptors (mGluRs) in regulating the activity of GCs in slices from wildtype and mGluR-/- mutant mice. In wildtype mice, bath application of the selective Group I mGluR agonist DHPG depolarized and increased the firing rate of both GC subtypes. In the presence of blockers of fast synaptic transmission (APV, CNQX, gabazine), DHPG directly depolarized both GC subtypes, although the two GC subtypes responded differentially to DHPG in mGluR1-/- and mGluR5-/- mice. DHPG depolarized sGCs in slices from mGluR5-/- mice, although it had no effect on sGCs in slices from mGluR1-/- mice. By contrast, DHPG depolarized dGCs in slices from mGluR1-/- mice but had no effect on dGCs in slices from mGluR5-/- mice. Previous studies showed that mitral cells express mGluR1 but not mGluR5. The present results therefore suggest that sGCs are more similar to mitral cells than dGCs in terms of mGluR expression.     

Differential plasma membrane distribution of metabotropic glutamate receptors mGluR1α, mGluR2 and mGluR5, relative to neurotransmitter release sites

Two group I metabotropic glutamate receptor subtypes, mGluR1 and mGluR5, have been reported to occur in highest concentration in an annulus surrounding the edge of the postsynaptic membrane specialisation. In order to determine whether such a distribution is uniform amongst postsynaptic mGluRs, their distribution was compared quantitatively by a pre-embedding silver-intensified immunogold technique at electron microscopic level in hippocampal pyramidal cells (mGluR5), cerebellar Purkinje cells (mGluR1α) and Golgi cells (mGluR2). The results show that mGluR1α, mGluR5 and mGluR2 each have a distinct distribution in relation to the glutamatergic synaptic junctions. On dendritic spines, mGluR1α and mGluR5 showed the highest receptor density in a perisynaptic annulus (defined as within 60 nm of the edge of the synapse) followed by a decreasing extrasynaptic (60–900 nm) receptor level, but the gradient of decrease and the proportion of the perisynaptic pool (mGluR1α, 50%; vs mGluR5, 25%) were different for the two receptors. The distributions of mGluR1α and mGluR5 also differed significantly from simulated random distributions. In contrast, mGluR2 was not closely associated with glutamatergic synapses in the dendritic plasma membrane of cerebellar Golgi cells and its distribution relative to synapses is not different from simulated random distribution in the membrane. The somatic membrane, the axon and the synaptic boutons of the GABAergic Golgi cells also contained immunoreactive mGluR2 that is not associated with synaptic specialisations. In the hippocampal CA1 area the distribution of immunoparticles for mGluR5 on individual spines was established using serial sections. The results indicate that dendritic spines of pyramidal cells are heterogeneous with respect to the ratio of perisynaptic to extrasynaptic mGluR5 pools and about half of the immunopositive spines lack the perisynaptic pool. The quantitative comparison of receptor distributions demonstrates that mGluR1α and mGluR5, but not mGluR2, are highly compartmentalised in different plasma membrane domains. The unique distribution of each mGluR subtype may reflect requirements for different transduction and effector mechanisms between cell types and different domains of the same cell, and suggests that the precise placement of receptors is a crucial factor contributing to neuronal communication.     

Distribution and synaptic localisation of the metabotropic glutamate receptor 4 (mGluR4) in the rodent CNS

Group III metabotropic glutamate receptors (mGluRs) are selectively activated by L-2-amino-4-phosphonobutyrate (L-AP4), which produces depression of synaptic transmission. The relative contribution of different group III mGluRs to the effects of L-AP4 remains to be clarified. Here, we assessed the distribution of mGluR4 in the rat and mouse brain using affinity-purified antibodies raised against its entire C-terminal domain. The antibodies reacted specifically with mGluR4 and not with other mGluRs in transfected COS 7 cells. No immunoreactivity was detected in brains of mice with gene-targeted deletion of mGluR4. Pre-embedding immunocytochemistry for light and electron microscopy showed the most intense labelling in the cerebellar cortex, basal ganglia, the sensory relay nuclei of the thalamus, and some hippocampal areas. Immunolabelling was most intense in presynaptic active zones. In the basal ganglia, both the direct and indirect striatal output pathways showed immunolabelled terminals forming mostly type II synapses on dendritic shafts. The localisation of mGluR4 on GABAergic terminals of striatal projection neurones suggests a role as a presynaptic heteroreceptor. In the cerebellar cortex and hippocampus, mGluR4 was also localised in terminals establishing type I synapses, where it probably operates as an autoreceptor. In the hippocampus, mGluR4 labelling was prominent in the dentate molecular layer and CA1-3 strata lacunosum moleculare and oriens. Somatodendritic profiles of some stratum oriens/alveus interneurones were richly decorated with mGluR4-labelled axon terminals making either type I or II synapses. This differential localisation suggests a regulation of synaptic transmission via a target cell-dependent synaptic segregation of mGluR4.Our results demonstrate that, like other group III mGluRs, presynaptic mGluR4 is highly enriched in the active zone of boutons innervating specific classes of neurones. In addition, the question of alternatively spliced mGluR4 isoforms is discussed.     

Activation of group I metabotropic glutamate receptors leads to brain-derived neurotrophic factor expression in rat C6 cells

Brain-derived neurotrophic factor (BDNF), which mediates neuronal growth, neuroprotection and synaptic modulation, is expressed in neurons and glial cells. The present study investigated the expression of BDNF in response to the activation of group I metabotropic glutamate receptors (mGluRs) by (S)-3,5-Dihydroxyphenylglycine (DHPG) in rat C6 glioma cells. The increase in BDNF mRNA in DHPG-stimulated cells, which peaked by 12 h after DHPG exposure, was attenuated by the mGluR5 inhibitor MPEP, but not by the mGluR1 inhibitor CPCCOEt. DHPG-induced BDNF mRNA expression reduced in cultures pretreated with protein kinase C (PKC) inhibitor, GFX, but not with calcium/calmodulin kinase II (CaMKII) inhibitor, KN-93. Immunostaining revealed high BDNF expression in cytoplasm of C6 cells after 48 h of incubation with 1 μM DHPG, but this was lower in MPEP-pretreated cells. These results indicate that activation of group I mGluRs induces BDNF mRNA and protein expression via mGluR5 subtype and PKC-dependent signaling pathway in C6 glioma cells.     

Reduction of excitatory postsynaptic responses by persistently active metabotropic glutamate receptors in the hippocampus

The release of glutamate from axon terminals is under the control of a variety of presynaptic receptors, including several metabotropic glutamate receptors (mGluRs). Synaptically released glutamate can activate mGluRs within the same synapse where it was released and also at a distance following its diffusion from the synaptic cleft. It is unknown, however, whether the release of glutamate is under the control of persistently active mGluRs. We tested the contribution of mGluR activation to the excitatory postsynaptic responses recorded from several types of GABAergic interneuron in strata oriens/alveus of the mouse hippocampus. The application of 1 microM (alphaS)-alpha-amino-alpha-[(1S,2S)-2-carboxycyclopropyl]xanthine-9-propanoic acid (LY341495), a broad-spectrum mGluR (subtypes 2/3/7/8) antagonist at this concentration, increased evoked-excitatory postsynaptic current (eEPSC) amplitudes by 60% (n = 33). On identified cell types, LY341495 had either no effect (7 of 14 basket and 7 of 13 oriens-lacunosum moleculare, O-LM cells) or resulted in a 32 +/- 30% (mean +/- SD) increase in EPSC amplitudes recorded from basket cells and a seven-times greater (216 +/- 102%) enhancement of EPSCs in O-LM cells. The enhancement of the first EPSC of a high-frequency train indicates persistent mGluR activation. During antagonist application, the relative increase in EPSC amplitude evoked by the second and subsequent pulses in the train was not larger than that of the first EPSC, showing no further receptor activation by the released transmitter. The effect of mGluR subtype selective agonists [3 microM L(+)-2-amino-4-phosphonobutyric acid (L-AP4): mGluR4/8; 600 microM L-AP4: mGluR4/7/8; 1 microM (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IU): mGluR2/3] and an antagonist (0.2 microM LY341495: mGluR2/3/8) suggests that persistently active mGluR2/3/8 control the excitability of hippocampal network.     

Metabotropic glutamate receptor 1 promotes cementoblast proliferation via MAP kinase signaling pathways

Purpose/aim: Glutamate is one of the signaling molecules responsible for transmission in the central nervous system. Periodontal ligament (PDL) cells were recently reported to express metabotropic glutamate receptors (mGluRs). However, the functions of mGluR signaling in PDL cells or PDL-related cells remain largely unknown. The aim of this study was to investigate the expression and function of mGluRs in PDL-related cells. Materials and methods: OCCM-30 cells, immortalized murine cementoblasts, were stimulated with l-glutamate or mGluRs antagonists. The cells’ proliferative response was evaluated using a colorimetric assay and gene expression was assessed using real-time polymerase chain reaction. The nuclear translocation of cyclin D1 was evaluated by immunohistochemistry. Results: l-Glutamate promoted the proliferation of OCCM-30 cells, which expressed mGluR1, but not mGluR5. Dihydroxyphenylglycine (DHPG), an agonist of group I mGluRs (mGluR1 and mGluR5), also promoted cell proliferation, and this was inhibited by LY456236, an mGluR1 antagonist. DHPG increased the expression of cyclin D1, a key regulator of cell proliferation, and its nuclear translocation. DHPG also increased the expression of Bcl2A1, an antiapoptotic oncogene and simultaneously reduced the expression of Bax, a pro-apoptotic marker. Furthermore, the DHPG-induced proliferation of OCCM-30 cells was reduced by pretreatment with SB203580, SP600125, and PD98059, inhibitors of p38, JNK, and ERK1/2, respectively. Conclusions: These findings indicate that activation of mGluR1 expressed by OCCM-30 cells induces cell proliferation in a manner that is dependent on mitogen-activated protein kinase pathways and that cyclin D1 and Bcl2A1/Bax may be involved. Our results provide useful information for elucidating the mechanisms underlying cementum homeostasis and regeneration.     

Groups II and III metabotropic glutamate receptors differentially modulate brief and prolonged nociception in primate STT cells

The heterogeneous family of G-protein-coupled metabotropic glutamate receptors (mGluRs) provides excitatory and inhibitory controls of synaptic transmission and neuronal excitability in the nervous system. Eight mGluR subtypes have been cloned and are classified in three subgroups. Group I mGluRs can stimulate phosphoinositide hydrolysis and activate protein kinase C whereas group II (mGluR2 and 3) and group III (mGluR4, 6, 7, and 8) mGluRs share the ability to inhibit cAMP formation. The present study examined the roles of groups II and III mGluRs in the processing of brief nociceptive information and capsaicin-induced central sensitization of primate spinothalamic tract (STT) cells in vivo. In 11 anesthetized male monkeys (Macaca fascicularis), extracellular recordings were made from 21 STT cells in the lumbar dorsal horn. Responses to brief (15 s) cutaneous stimuli of innocuous (brush), marginally and distinctly noxious (press and pinch, respectively) intensity were recorded before, during, and after the infusion of group II and group III mGluR agonists into the dorsal horn by microdialysis. Different concentrations were applied for at least 20 min each (at 5 microliter/min) to obtain cumulative concentration-response relationships. Values in this paper refer to the drug concentrations in the microdialysis fibers; actual concentrations in the tissue are about three orders of magnitude lower. The agonists were also applied at 10-25 min after intradermal capsaicin injection. The group II agonists (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (LCCG1, 1 microM-10 mM, n = 6) and (-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4, 6-dicarboxylate (LY379268; 1 microM-10 mM, n = 6) had no significant effects on the responses to brief cutaneous mechanical stimuli (brush, press, pinch) or on ongoing background activity. In contrast, the group III agonist L(+)-2-amino-4-phosphonobutyric acid (LAP4, 0. 1 microM-10 mM, n = 6) inhibited the responses to cutaneous mechanical stimuli in a concentration-dependent manner, having a stronger effect on brush responses than on responses to press and pinch. LAP4 did not change background discharges significantly. Intradermal injections of capsaicin increased ongoing background activity and sensitized the STT cells to cutaneous mechanical stimuli (ongoing activity > brush > press > pinch). When given as posttreatment, the group II agonists LCCG1 (100 microM, n = 5) and LY379268 (100 microM, n = 6) and the group III agonist LAP4 (100 microM, n = 6) reversed the capsaicin-induced sensitization. After washout of the agonists, the central sensitization resumed. Our data suggest that, while activation of both group II and group III mGluRs can reverse capsaicin-induced central sensitization, it is the actions of group II mGluRs in particular that undergo significant functional changes during central sensitization because they modulate responses of sensitized STT cells but have no effect under control conditions.     

Cellular localization of metabotropic glutamate receptors mGluR1, 2/3, 5 and 7 in the main and accessory olfactory bulb of the rat.

The cellular localization of metabotropic glutamate receptors (mGluRs) (mGluR1alpha, 2/3, 5a and 7) in the main and accessory olfactory bulb (MOB and AOB) of adult rats was compared by using affinity purified polyclonal antibodies directed to their C-termini. mGluR1alpha and mGluR5a immunoreactivities were located in comparable structures of the MOB and AOB with different levels of intensity. mGluR5a reactivity was high in the AOB. mGluR2/3 showed a different pattern of expression in the MOB compared to that observed in the AOB; the periglomerular region of the MOB was strongly stained, but in the AOB it was the mitral/tufted cell layer that was intense. The mitral cell bodies in the MOB were strongly immunoreactive for mGluR7. These differences in the distribution of mGluRs in the MOB and AOB may reflect differences in synaptic transmission and sensitivity to neuromodulation in the two systems.     

Spatially distinct actions of metabotropic glutamate receptor activation in dorsal lateral geniculate nucleus

Thalamocortical neurons in the dorsal lateral geniculate nucleus (dLGN) dynamically communicate visual information from the retina to the neocortex, and this process can be modulated via activation of metabotropic glutamate receptors (mGluRs). Neurons within dLGN express different mGluR subtypes associated with distinct afferent synaptic pathways; however, the physiological function of this organization is unclear. We report that the activation of mGluR(5), which are located on presynaptic dendrites of local interneurons, increases GABA output that in turn produces an increased inhibitory activity on proximal but not distal dendrites of dLGN thalamocortical neurons. In contrast, mGluR(1) activation produces strong membrane depolarization in thalamocortical neurons regardless of distal or proximal dendritic locations. These findings provide physiological evidence that mGluR(1) appear to be distributed along the thalamocortical neuron dendrites, whereas mGluR(5)-dependent action occurs on the proximal dendrites/soma of thalamocortical neurons. The differential distribution and activation of mGluR subtypes on interneurons and thalamocortical neurons may serve to shape excitatory synaptic integration and thereby regulate information gating through the thalamus.