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I Metabotropic Glutamate Receptors (i + metabotropic_glutamate_receptor)
Kinds of I Metabotropic Glutamate Receptors Selected AbstractsActivation of class I metabotropic glutamate receptors limits dendritic growth of Purkinje cells in organotypic slice culturesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2006Alexandra Sirzen-Zelenskaya Abstract The development of the dendritic tree of a neuron is a complex process which is thought to be regulated strongly by signals from afferent fibers. We showed previously that the blockade of glutamatergic excitatory neurotransmission has little effect on Purkinje cell dendritic development. We have now studied the effects of glutamate receptor agonists on the development of Purkinje cell dendrites in mouse organotypic slice cultures. The activation of N -methyl- d -aspartate receptors had no major effect on Purkinje cell dendrites and the activation of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid receptors was strongly excitotoxic so that no analysis of its effects on dendritic development was possible. The activation of metabotropic glutamate receptors led to a very strong inhibition of dendritic growth, resulting in Purkinje cells with very small stubby dendrites. This effect was specific for the activation of class I metabotropic glutamate receptors and could not be reduced by blocking synaptic transmission in the cultures, indicating that it was mediated by receptors present on Purkinje cells. Pharmacological experiments suggest that the signaling pathway involved does not require activation of phospholipase C or protein kinase C. The inhibition of dendritic growth by activation of class I metabotropic glutamate receptor could be a useful negative feedback mechanism for limiting the size of the dendritic tree of Purkinje cells after the establishment of a sufficient number of parallel fiber contacts. This developmental mechanism could protect Purkinje cells from excitotoxic death through excessive release of glutamate from an overload of parallel fiber contacts. [source] Developmental shift from long-term depression to long-term potentiation in the rat medial vestibular nuclei: role of group I metabotropic glutamate receptorsTHE JOURNAL OF PHYSIOLOGY, Issue 2 2003Julien Puyal The effects of high frequency stimulation (HFS) of the primary vestibular afferents on synaptic transmission in the ventral part of the medial vestibular nuclei (vMVN) were studied during postnatal development and compared with the changes in the expression of the group I metabotropic glutamate receptor (mGluR) subtypes, mGluR1 and mGluR5. During the first stages of development, HFS always induced a mGluR5- and GABAA -dependent long-term depression (LTD) which did not require NMDA receptor and mGluR1 activation. The probability of inducing LTD decreased progressively throughout the development and it was zero at about the end of the second postnatal week. Conversely, long-term potentiation (LTP) appeared at the beginning of the second week and its occurrence increased to reach the adult value at the end of the third week. Of interest, the sudden change in the LTP frequency occurred at the time of eye opening, about the end of the second postnatal week. LTP depended on NMDA receptor and mGluR1 activation. In parallel with the modifications in synaptic plasticity, we observed that the expression patterns and localizations of mGluR5 and mGluR1 in the medial vestibular nuclei (MVN) changed during postnatal development. At the earlier stages the mGluR1 expression was minimal, then increased progressively. In contrast, mGluR5 expression was initially high, then decreased. While mGluR1 was exclusively localized in neuronal compartments and concentrated at the postsynaptic sites at all stages observed, mGluR5 was found mainly in neuronal compartments at immature stages, then preferentially in glial compartments at mature stages. These results provide the first evidence for a progressive change from LTD to LTP accompanied by a distinct maturation expression of mGluR1 and mGluR5 during the development of the MVN. [source] Activation of class I metabotropic glutamate receptors limits dendritic growth of Purkinje cells in organotypic slice culturesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2006Alexandra Sirzen-Zelenskaya Abstract The development of the dendritic tree of a neuron is a complex process which is thought to be regulated strongly by signals from afferent fibers. We showed previously that the blockade of glutamatergic excitatory neurotransmission has little effect on Purkinje cell dendritic development. We have now studied the effects of glutamate receptor agonists on the development of Purkinje cell dendrites in mouse organotypic slice cultures. The activation of N -methyl- d -aspartate receptors had no major effect on Purkinje cell dendrites and the activation of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid receptors was strongly excitotoxic so that no analysis of its effects on dendritic development was possible. The activation of metabotropic glutamate receptors led to a very strong inhibition of dendritic growth, resulting in Purkinje cells with very small stubby dendrites. This effect was specific for the activation of class I metabotropic glutamate receptors and could not be reduced by blocking synaptic transmission in the cultures, indicating that it was mediated by receptors present on Purkinje cells. Pharmacological experiments suggest that the signaling pathway involved does not require activation of phospholipase C or protein kinase C. The inhibition of dendritic growth by activation of class I metabotropic glutamate receptor could be a useful negative feedback mechanism for limiting the size of the dendritic tree of Purkinje cells after the establishment of a sufficient number of parallel fiber contacts. This developmental mechanism could protect Purkinje cells from excitotoxic death through excessive release of glutamate from an overload of parallel fiber contacts. [source] IP3 receptor in the hair cells of frog semicircular canal and its possible functional roleEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2006Maria Lisa Rossi Abstract The presence and functional role of inositol trisphosphate receptors (IP3R) was investigated by electrophysiology and immunohistochemistry in hair cells from the frog semicircular canal. Intracellular recordings were performed from single fibres of the posterior canal in the isolated, intact frog labyrinth, at rest and during rotation, in the presence of IP3 receptor inhibitors and drugs known to produce Ca2+ release from the internal stores or to increase IP3 production. Hair cell immunolabelling for IP3 receptor was performed by standard procedures. The drug 2-aminoethoxydiphenyl borate (2APB), an IP3 receptor inhibitor, produced a marked decrease of mEPSP and spike frequency at low concentration (0.1 mm), without affecting mEPSP size or time course. At high concentration (1 mm), 2APB is reported to block the sarcoplasmic-endoplasmic reticulum Ca2+ -ATPase (SERCA pump) and increase [Ca2+]i; at the labyrinthine cytoneural junction, it greatly enhanced the resting and mechanically evoked sensory discharge frequency. The selective agonist of group I metabotropic glutamate receptors (RS)-3,5-dihydroxyphenylglycine (DHPG, 0.6 mm), produced a transient increase in resting mEPSP and spike frequency at the cytoneural junction, with no effects on mEPSP shape or amplitude. Pretreatment with cyclopiazonic acid (CPA, 0.1 mm), a SERCA pump inhibitor, prevented the facilitatory effect of both 2APB and DHPG, suggesting a link between Ca2+ release from intracellular stores and quantal emission. Consistently, diffuse immunoreactivity for IP3 receptors was observed in posterior canal hair cells. Our results indicate the presence and a possibly relevant functional role of IP3-sensitive stores in controlling [Ca2+]i and modulating the vestibular discharge. [source] Regulation of Homer and group I metabotropic glutamate receptors by nicotineEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2005J. K. Kane Abstract The present study focuses on the nicotine-induced modulation of mRNA and protein expression of a number of genes involved in glutamatergic synaptic transmission in rat brain over different time periods of exposure. A subchronic (3 days) but not the chronic (7 or 14 days) administration of nicotine resulted in the up-regulation of Homer2a/b mRNA in the amygdala while in the ventral tegmental area (VTA) no change in expression of either Homer2a/b or Homer1b/c was observed. Although the increase in Homer2a/b mRNA was not translated into the protein level in the amygdala, a slight but significant up-regulation of Homer1b/c protein was observed in the same region at day 3. Both Homer forms were up-regulated at the protein level in the VTA at day 3. In the nucleus accumbens, 14 days of nicotine treatment up-regulated mRNA of Homer2b/c by 68.2% (P < 0.05), while the short form Homer1a gene was down-regulated by 65.0% at day 3 (P < 0.05). In regard to other components of the glutamatergic signalling, we identified an acute and intermittent increase in the mRNA and protein levels of mGluR1 and mGluR5 in the amygdala. In the VTA, however, the effects of nicotine on mGluR mRNA expression were long-lasting but rather specific to mGluR1. Nevertheless, mGluR1 protein levels in the VTA area were up-regulated only at day 3, as in the amygdala. These data provide further evidence for the involvement of nicotine in the glutamatergic neuronal synaptic activity in vivo, suggesting a role for the newly identified Homer proteins in this paradigm. [source] Group I metabotropic glutamate receptors regulate the frequency,response function of hippocampal CA1 synapses for the induction of LTP and LTDEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2004Els J. M. Van Dam Abstract Synaptically released glutamate binds to ionotropic or metabotropic glutamate receptors. Metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors and can be divided into three subclasses (Group I,III) depending on their pharmacology and coupling to signal transduction cascades. Group I mGluRs are coupled to phospholipase C and are implicated in several important physiological processes, including activity-dependent synaptic plasticity, but their exact role in synaptic plasticity remains unclear. Synaptic plasticity can manifest itself as an increase or decrease of synaptic efficacy, referred to as long-term potentiation (LTP) and long-term depression (LTD). The likelihood, degree and direction of the change in synaptic efficacy depends on the history of the synapse and is referred to as ,metaplasticity'. We provide direct experimental evidence for an involvement of group I mGluRs in metaplasticity in CA1 hippocampal synapses. Bath application of a low concentration of the specific group I agonist 3,5-dihydroxyphenylglycine (DHPG), which does not affect basal synaptic transmission, resulted in a leftward shift of the frequency,response function for the induction of LTD and LTP in naïve synapses. DHPG resulted in the induction of LTP at frequencies which induced LTD in control slices. These alterations in the induction of LTD and LTP resemble the metaplastic changes observed in previously depressed synapses. In addition, in the presence of DHPG additional potentiation could be induced after LTP had apparently been saturated. These findings provide strong evidence for an involvement of group I mGluRs in the regulation of metaplasticity in the CA1 field of the hippocampus. [source] Dual effect of DL -homocysteine and S -adenosylhomocysteine on brain synthesis of the glutamate receptor antagonist, kynurenic acidJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2005E. Luchowska Abstract Increased serum level of homocysteine, a sulfur-containing amino acid, is considered a risk factor in vascular disorders and in dementias. The effect of homocysteine and metabolically related compounds on brain production of kynurenic acid (KYNA), an endogenous antagonist of glutamate ionotropic receptors, was studied. In rat cortical slices, DL -homocysteine enhanced (0.1,0.5 mM) or inhibited (concentration inducing 50% inhibition [IC50] = 6.4 [5.5,7.5] mM) KYNA production. In vivo peripheral application of DL -homocysteine (1.3 mmol/kg intraperitoneally) increased KYNA content (pmol/g tissue) from 8.47 ± 1.57 to 13.04 ± 2.86 (P < 0.01; 15 min) and 11.4 ± 1.72 (P < 0.01; 60 min) in cortex, and from 4.11 ± 1.54 to 10.02 ± 3.08 (P < 0.01; 15 min) in rat hippocampus. High concentrations of DL -homocysteine (20 mM) applied via microdialysis probe decreased KYNA levels in rabbit hippocampus; this effect was antagonized partially by an antagonist of group I metabotropic glutamate receptors, LY367385. In vitro, S -adenosylhomocysteine acted similar to but more potently than DL -homocysteine, augmenting KYNA production at 0.03,0.08 mM and reducing it at ,0.5 mM. The stimulatory effect of S -adenosylhomocysteine was abolished in the presence of the L -kynurenine uptake inhibitors L -leucine and L -phenyloalanine. Neither the N -methyl- D -aspartate (NMDA) antagonist CGS 19755 nor L -glycine influenced DL -homocysteine- and S -adenosylhomocysteine-induced changes of KYNA synthesis in vitro. DL -Homocysteine inhibited the activity of both KYNA biosynthetic enzymes, kynurenine aminotransferases (KATs) I and II, whereas S -adenosylhomocysteine reduced only the activity of KAT II. L -Methionine and L -cysteine, thiol-containing compounds metabolically related to homocysteine, acted only as weak inhibitors, reducing KYNA production in vitro and inhibiting the activity of KAT II (L -cysteine) or KAT I (L -methionine). The present data suggest that DL -homocysteine biphasically modulates KYNA synthesis. This seems to result from conversion of compound to S -adenosylhomocysteine, also acting dually on KYNA formation, and in part from the direct interaction of homocysteine with metabotropic glutamate receptors and KYNA biosynthetic enzymes. It seems probable that hyperhomocystemia-associated brain dysfunction is mediated partially by changes in brain KYNA level. © 2004 Wiley-Liss, Inc. [source] Roles of distinct glutamate receptors in induction of anti-Hebbian long-term potentiationTHE JOURNAL OF PHYSIOLOGY, Issue 6 2008Dimitri M. Kullmann Many glutamatergic synapses on interneurons involved in feedback inhibition in the CA1 region of the hippocampus exhibit an unusual form of long-term potentiation (LTP) that is induced only if presynaptic glutamate release occurs when the postsynaptic membrane potential is relatively hyperpolarized. We have named this phenomenon ,anti-Hebbian' LTP because it is prevented by postsynaptic depolarization during afferent activity, and hence its induction requirements are opposite to those of Hebbian NMDA receptor-dependent LTP. This symposium report addresses the roles of distinct glutamate receptors in the induction of anti-Hebbian LTP. Inwardly rectifying Ca2+ -permeable AMPA receptors mediate fast glutamatergic signalling at synapses that exhibit this form of LTP, and they are highly likely to mediate the instructive signal that triggers the cascade leading to synapse strengthening. NMDA receptors, on the other hand, play no role, nor do they contribute substantially to synaptic transmission at synapses that exhibit anti-Hebbian LTP. Both kainate and group I metabotropic glutamate receptors are abundant in at least some interneurons in the feedback inhibitory circuit. Delineating the roles of kainate receptors has been hampered by sub-optimal pharmacological tools. As for group I metabotropic glutamate receptors, their role in anti-Hebbian LTP is permissive at the very least in some interneuron types, although an instructive role has been suggested in other forms of activity-dependent plasticity. [source] Developmental shift from long-term depression to long-term potentiation in the rat medial vestibular nuclei: role of group I metabotropic glutamate receptorsTHE JOURNAL OF PHYSIOLOGY, Issue 2 2003Julien Puyal The effects of high frequency stimulation (HFS) of the primary vestibular afferents on synaptic transmission in the ventral part of the medial vestibular nuclei (vMVN) were studied during postnatal development and compared with the changes in the expression of the group I metabotropic glutamate receptor (mGluR) subtypes, mGluR1 and mGluR5. During the first stages of development, HFS always induced a mGluR5- and GABAA -dependent long-term depression (LTD) which did not require NMDA receptor and mGluR1 activation. The probability of inducing LTD decreased progressively throughout the development and it was zero at about the end of the second postnatal week. Conversely, long-term potentiation (LTP) appeared at the beginning of the second week and its occurrence increased to reach the adult value at the end of the third week. Of interest, the sudden change in the LTP frequency occurred at the time of eye opening, about the end of the second postnatal week. LTP depended on NMDA receptor and mGluR1 activation. In parallel with the modifications in synaptic plasticity, we observed that the expression patterns and localizations of mGluR5 and mGluR1 in the medial vestibular nuclei (MVN) changed during postnatal development. At the earlier stages the mGluR1 expression was minimal, then increased progressively. In contrast, mGluR5 expression was initially high, then decreased. While mGluR1 was exclusively localized in neuronal compartments and concentrated at the postsynaptic sites at all stages observed, mGluR5 was found mainly in neuronal compartments at immature stages, then preferentially in glial compartments at mature stages. These results provide the first evidence for a progressive change from LTD to LTP accompanied by a distinct maturation expression of mGluR1 and mGluR5 during the development of the MVN. [source] | ||||||||||