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https://www.readbyqxmd.com/read/27886171/transduction-of-group-i-mglur-mediated-synaptic-plasticity-by-%C3%AE-arrestin2-signalling
#1
Andrew G Eng, Daniel A Kelver, Tristan P Hedrick, Geoffrey T Swanson
Conventional signalling by the group I metabotropic glutamate receptors, mGluR1 and mGluR5, occurs through G-protein coupling, but evidence suggests they might also utilize other, non-canonical effector pathways. Here we test whether group I mGluRs require β-arrestin signalling during specific forms of plasticity at hippocampal excitatory synapses. We find that genetic ablation of β-arrestin2, but not β-arrestin1, results in deficits in plasticity mediated by mGlu1 receptors in CA3 pyramidal neurons and by mGlu5 receptors in CA1 pyramidal neurons...
November 25, 2016: Nature Communications
https://www.readbyqxmd.com/read/27880915/blunted-mglur-activation-disinhibits-striatopallidal-transmission-in-parkinsonian-mice
#2
Qiaoling Cui, Jason E Pitt, Arin Pamukcu, Jean-Francois Poulin, Omar S Mabrouk, Michael P Fiske, Isabel B Fan, Elizabeth C Augustine, Katherine A Young, Robert T Kennedy, Rajeshwar Awatramani, C Savio Chan
The prevailing circuit model predicts that hyperactivity of the striatopallidal pathway and subsequently increased inhibition of external globus pallidus (GPe) neurons lead to the hypokinetic symptoms of Parkinson's disease (PD). It is believed that hyperactivity of the striatopallidal pathway is due to inactivity of dopamine receptors on the somatodendritic membrane of striatopallidal neurons, but the exact cellular underpinnings remain unclear. In this study, we show that mouse GPe astrocytes critically control ambient glutamate level, which in turn gates striatopallidal transmission via the activation of presynaptic metabotropic glutamate receptors...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27872582/separate-ionotropic-and-metabotropic-glutamate-receptor-functions-in-depotentiation-vs-ltp-a-distinct-role-for-group1-mglur-subtypes-and-nmdars
#3
Amira Latif-Hernandez, Enrico Faldini, Tariq Ahmed, Detlef Balschun
Depotentiation (DP) is a mechanism by which synapses that have recently undergone long-term potentiation (LTP) can reverse their synaptic strengthening within a short time-window after LTP induction. Group 1 metabotropic glutamate receptors (mGluRs) were shown to be involved in different forms of LTP and long-term depression (LTD), but little is known about their roles in DP. Here, we generated DP by applying low-frequency stimulation (LFS) at 5 Hz after LTP had been induced by a single train of theta-burst-stimulation (TBS)...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27872019/metabotropic-glutamate-receptors-and-neurodegenerative-diseases
#4
REVIEW
Fabiola M Ribeiro, Luciene B Vieira, Rita G W Pires, Roenick P Olmo, Stephen S G Ferguson
Glutamate is the most important excitatory neurotransmitter of the mammalian central nervous system (CNS), playing an important role in memory, synaptic plasticity and neuronal development. However, glutamate overstimulation is also implicated in neuronal cell death. There are two major types of glutamate receptors: ionotropic and metabotropic. Thus far, eight metabotropic glutamate receptors (mGluRs) subtypes have been characterized and are divided into three subgroups based on sequence homology and cell signaling activation...
November 19, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27866902/the-atypical-antipsychotic-olanzapine-disturbs-depotentiation-by-modulating-machrs-and-impairs-reversal-learning
#5
Woo Seok Song, Jin Hee Cha, Sang Ho Yoon, Young Seon Cho, Kyeong-Yeol Park, Myoung-Hwan Kim
Antipsychotic medication is an essential component for treating schizophrenia, which is a serious mental disorder that affects approximately 1% of the global population. Olanzapine (Olz), one of the most frequently prescribed atypical antipsychotics, is generally considered a first-line drug for treating schizophrenia. In contrast to psychotic symptoms, the effects of Olz on cognitive symptoms of schizophrenia are still unclear. In addition, the mechanisms by which Olz affects the neural circuits associated with cognitive function are unknown...
November 17, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27856517/mglur-long-term-depression-regulates-glua2-association-with-copii-vesicles-and-exit-from-the-endoplasmic-reticulum
#6
Joseph E Pick, Latika Khatri, Matheus F Sathler, Edward B Ziff
mGluR long-term depression (mGluR-LTD) is a form of synaptic plasticity induced at excitatory synapses by metabotropic glutamate receptors (mGluRs). mGluR-LTD reduces synaptic strength and is relevant to learning and memory, autism, and sensitization to cocaine; however, the mechanism is not known. Here we show that activation of Group I mGluRs in medium spiny neurons induces trafficking of GluA2 from the endoplasmic reticulum (ER) to the synapse by enhancing GluA2 binding to essential COPII vesicle proteins, Sec23 and Sec13...
November 17, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27847432/metabotropic-glutamate-receptor-dependent-long-term-depression-in-the-cortex
#7
REVIEW
Sukjae Joshua Kang, Bong-Kiun Kaang
Metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD), a type of synaptic plasticity, is characterized by a reduction in the synaptic response, mainly at the excitatory synapses of the neurons. The hippocampus and the cerebellum have been the most extensively studied regions in mGluR-dependent LTD, and Group 1 mGluR has been reported to be mainly involved in this synaptic LTD at excitatory synapses. However, mGluR-dependent LTD in other brain regions may be involved in the specific behaviors or diseases...
November 2016: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/27807414/depotentiation-from-potentiated-synaptic-strength-in-a-tristable-system-of-coupled-phosphatase-and-kinase
#8
Mengjiao Chen, Wei Ren, Xingang Wang
Long-term potentiation (LTP) of synaptic strength is strongly implicated in learning and memory. On the other hand, depotentiation, the reversal of synaptic strength from potentiated LTP state to the pre-LTP level, is required in extinction of the obsolete memory. A generic tristable system, which couples the phosphatase and kinase switches, exclusively explains how moderate and high elevation of intracellular calcium concentration triggers long-term depression (LTD) and LTP, respectively. The present study, introducing calcium influx and calcium release from internal store into the tristable system, further show that significant elevation of cytoplasmic calcium concentration switches activation of both kinase and phosphatase to their basal states, thereby depotentiate the synaptic strength...
2016: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/27798131/cocaine-exposure-enhances-the-activity-of-ventral-tegmental-area-dopamine-neurons-via-calcium-impermeable-nmdars
#9
Meaghan Creed, Jennifer Kaufling, Giulia R Fois, Marion Jalabert, Tifei Yuan, Christian Lüscher, Francois Georges, Camilla Bellone
: Potentiation of excitatory inputs onto dopamine neurons of the ventral tegmental area (VTA) induced by cocaine exposure allows remodeling of the mesocorticolimbic circuitry, which ultimately drives drug-adaptive behavior. This potentiation is mediated by changes in NMDAR and AMPAR subunit composition. It remains unknown how this synaptic plasticity affects the activity of dopamine neurons. Here, using rodents, we demonstrate that a single cocaine injection increases the firing rate and bursting activity of VTA dopamine neurons, and that these increases persist for 7 d...
October 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27781556/mood-therapeutics-novel-pharmacological-approaches-for-treating-depression
#10
Ioline D Henter, Rafael T de Sousa, Philip W Gold, Andre R Brunoni, Carlos A Zarate, Rodrigo Machado-Vieira
Real-world effectiveness trials suggest that antidepressant efficacy is limited in many patients with mood disorders, underscoring the urgent need for novel therapeutics to treat these disorders. Areas Covered: Here, we review the clinical evidence supporting the use of novel modulators for the treatment of mood disorders, including specific glutamate modulators such as: 1) high-trapping glutamatergic modulators; 2) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists; 3) NMDA receptor glycine-site partial agonists; and 4) metabotropic glutamate receptor (mGluR) modulators...
October 26, 2016: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/27738636/activated-m%C3%A3-ller-cells-involved-in-atp-induced-upregulation-of-p2x7-receptor-expression-and-retinal-ganglion-cell-death
#11
Ying Xue, Yuting Xie, Bo Xue, Nan Hu, Guowei Zhang, Huaijin Guan, Min Ji
P2X7 receptor (P2X7R), an ATP-gated ion channel, plays an important role in glaucomatous retinal ganglion cell (RGC) apoptotic death, in which activated retinal Müller glial cells may be involved by releasing ATP. In the present study, we investigated whether and how activated Müller cells may induce changes in P2X7R expression in RGCs by using immunohistochemistry and Western blot techniques. Intravitreal injection of DHPG, a group I metabotropic glutamate receptor (mGluR I) agonist, induced upregulation of GFAP expression, suggestive of Müller cell activation (gliosis), as we previously reported...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27721389/neurodevelopmental-expression-profile-of-dimeric-and-monomeric-group-1-mglurs-relevance-to-schizophrenia-pathogenesis-and-treatment
#12
Jeremy S Lum, Francesca Fernandez, Natalie Matosin, Jessica L Andrews, Xu-Feng Huang, Lezanne Ooi, Kelly A Newell
Group 1 metabotropic glutamate receptors (mGluR1/mGluR5) play an integral role in neurodevelopment and are implicated in psychiatric disorders, such as schizophrenia. mGluR1 and mGluR5 are expressed as homodimers, which is important for their functionality and pharmacology. We examined the protein expression of dimeric and monomeric mGluR1α and mGluR5 in the prefrontal cortex (PFC) and hippocampus throughout development (juvenile/adolescence/adulthood) and in the perinatal phencyclidine (PCP) model of schizophrenia...
October 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27720859/involvement-of-p2x7-receptors-in-retinal-ganglion-cell-apoptosis-induced-by-activated-m%C3%A3-ller-cells
#13
Bo Xue, Yuting Xie, Ying Xue, Nan Hu, Guowei Zhang, Huaijin Guan, Min Ji
Müller cell reactivation (gliosis) is an early response in glaucomatous retina. Previous studies have demonstrated that activation of P2X7 receptors results in retinal ganglion cell (RGC) apoptosis. Here, the issues of whether and how activated Müller cells may contribute to RGC apoptosis through P2X7 receptors were investigated. Either intravitreal injection of (S)-3,5-dihydroxyphenylglycine (DHPG), a group I metabotropic glutamate receptor (mGluR I) agonist, in normal rat retinas, or DHPG treatment of purified cultured rat retinal Müller cells induced an increase in glial fibrillary acidic protein (GFAP) expression, indicative of Müller cell gliosis...
October 6, 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/27663134/chronic-but-not-acute-immobilization-stress-stably-enhances-hippocampal-ca1-metabotropic-glutamate-receptor-dependent-long-term-depression
#14
Tathagata Sengupta, Rishi Das, Sumantra Chattarji
Acute stress has been shown to facilitate but not increase metabotropic glutamate receptor (mGluR) mediated Long-Term Depression (LTD) in the hippocampus. However, the effect of chronic stress on mGluR dependent LTD has not been investigated. Moreover, whether stress leads to a transient modification LTD threshold or a more stable change in synaptic plasticity needs to be addressed. In the present study, we have explored the effects of both a ten-day long and a single day immobilization stress protocol on mGluR-LTD at the CA3:CA1synapse in the hippocampus of adult male Sprague-Dawley rats, a day after applying stress...
October 28, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27659109/impaired-bidirectional-nmda-receptor-dependent-synaptic-plasticity-in-the-dentate-gyrus-of-adult-female-fmr1-heterozygous-knockout-mice
#15
S Y Yau, C A Bostrom, J Chiu, C J Fontaine, S Sawchuk, A Meconi, R C Wortman, E Truesdell, A Truesdell, C Chiu, B N Hryciw, B D Eadie, M Ghilan, B R Christie
Fragile-X syndrome (FXS) is caused by the transcriptional repression of the Fmr1 gene resulting in loss of the Fragile-X mental retardation protein (FMRP). This leads to cognitive impairment in both male and female patients, however few studies have focused on the impact of FXS in females. Significant cognitive impairment has been reported in approximately 35% of women who exhibit a heterozygous Fmr1 gene mutation, however to date there is a paucity of information regarding the mechanistic underpinnings of these deficits...
September 19, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27641494/mechanism-of-assembly-and-cooperativity-of-homomeric-and-heteromeric-metabotropic-glutamate-receptors
#16
Joshua Levitz, Chris Habrian, Shashank Bharill, Zhu Fu, Reza Vafabakhsh, Ehud Y Isacoff
G protein-coupled receptors (GPCRs) mediate cellular responses to a wide variety of extracellular stimuli. GPCR dimerization may expand signaling diversity and tune functionality, but little is known about the mechanisms of subunit assembly and interaction or the signaling properties of heteromers. Using single-molecule subunit counting on class C metabotropic glutamate receptors (mGluRs), we map dimerization determinants and define a heterodimerization profile. Intersubunit fluorescence resonance energy transfer measurements reveal that interactions between ligand-binding domains control the conformational rearrangements underlying receptor activation...
October 5, 2016: Neuron
https://www.readbyqxmd.com/read/27633915/a-novel-form-of-capsaicin-modified-amygdala-ltd-mediated-by-trpm1
#17
Christine Gebhardt, Oliver von Bohlen Und Halbach, Michael D Hadler, Christian Harteneck, Doris Albrecht
Recently we have shown that capsaicin attenuates the strength of LTP in the lateral amygdala (LA) and demonstrated that this effect is mediated by the transient receptor potential (TRP) channel TRPV1. Here we further show that capsaicin, which is thought to act primarily through TRPV1, modifies long term depression (LTD) in the LA. Yet the application of various TRPV1 antagonists does not reverse this effect and it remains in TRPV1-deficient mice. In addition, voltage gated calcium channels, nitric oxide and CB1 receptors are not involved...
December 2016: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27631130/niclosamide-is-a-negative-allosteric-modulator-of-group-i-metabotropic-glutamate-receptors-implications-for-neuropathic-pain
#18
Ni Ai, Richard D Wood, Eric Yang, William J Welsh
PURPOSE: Novel therapeutics are greatly needed that target specific pathological receptors and pathways involved in Neuropathic Pain (NP). Extending our previous work published in this Journal on Group I metabotropic glutamate receptor (mGluR) modulators, we now investigate the therapeutic potential of niclosamide in modulating aberrant glutamate transmission in NP. METHOD: Calcium mobilization assays and cross-receptor selectivity experiments are conducted to characterize the pharmacological activity of niclosamide...
September 8, 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/27630571/presynaptic-release-regulating-mglu1-receptors-in-central-nervous-system
#19
REVIEW
Anna Pittaluga
Group I metabotropic glutamate (mGlu) receptors consists of mGlu1 and mGlu5 receptor subtypes. These receptors are widely distributed in the central nervous system (CNS), where they preferentially mediate facilitatory signaling in neurones and glial cells, mainly by favoring phospholipase (PLC) translocation. Based on the literature so far available, group I Metabotropic glutamate receptors (mGluRs) are preferentially expressed at the postsynaptic side of chemical synapsis, where they participate in the progression of the chemical stimulus...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27618534/opposite-effects-of-mglur1a-and-mglur5-activation-on-nucleus-accumbens-medium-spiny-neuron-dendritic-spine-density
#20
Kellie S Gross, Dieter D Brandner, Luis A Martinez, M Foster Olive, Robert L Meisel, Paul G Mermelstein
The group I metabotropic glutamate receptors (mGluR1a and mGluR5) are important modulators of neuronal structure and function. Although these receptors share common signaling pathways, they are capable of having distinct effects on cellular plasticity. We investigated the individual effects of mGluR1a or mGluR5 activation on dendritic spine density in medium spiny neurons in the nucleus accumbens (NAc), which has become relevant with the potential use of group I mGluR based therapeutics in the treatment of drug addiction...
2016: PloS One
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