Journal: The Journal of Biological Chemistry

Article Title: Striatal mGlu 5 -mediated synaptic plasticity is independently regulated by location-specific receptor pools and divergent signaling pathways

doi: 10.1016/j.jbc.2023.104949

Figure Lengend Snippet: Striatal DHPG-LTD is sensitive to rapamycin but not to anisomycin . A , LFS (1 Hz × 900 pulses) induced LTD in slices from mGlu 5 WT striata which was inhibited by MPEP ( closed bar and circles ) but not by LY53 ( gray bar and circles ). B , DHPG-LTD was induced by 15 min administration of DHPG ( open bar ) in slices from mGlu 5 WT mice ( open circles ) but not from mGlu 5 KO mice ( closed squares ). C–F , effects of various drugs on DHPG-LTD in slices from WT mice. In ( C ), DHPG-LTD was blocked by MPEP ( black triangles ) and LY53 ( gray circles ) in the presence of CPCCOEt, all administered 5 min prior to DHPG. D , U0126 was continuously administered before and during the entire recording. In ( E ), anisomycin was administered 30 min prior to DHPG, whereas the doses indicated of rapamycin ( F ) were administered 5 min prior to DHPG. B and C , average DHPG-induced LTD was significantly blocked in KO slices and by MPEP and LY53 in time-matched striatal slices (75–90 min); U0126, anisomycin, and 20 nM rapamycin did not significantly affect DHPG-LTD, whereas 1 μM completely blocked it. Values represent the mean ± SEM; n = 5 to 7 slices per treatment. mGlu5, metabotropic glutamate receptor 5; LTD, long-term depression; LFS, low frequency stimulation.

Article Snippet: (+)-α-amino-3,5-dioxo-1,2,4-oxadiazolidine-2-propanoic acid, Quis, DHPG, MPEP, CPCCOEt, (±)-4-(4-aminophenyl)-1,2-dihydro-1-methyl-2-propylcarbamoyl-6,7-methylenedioxyphthalazine (SYM2206), d-2-amino-5-phosphonopentanoic acid (APV), CNQX, 2-amino-(N,N)-1-bis(hexadecahydro-6,13-diisopropyl-2,5,9-trimethyl-1,4,7,11,14-pentaoxo-1H-pyrrolo[2,1]-[1,4,7,10,13] oxatetraazacyclohexadecin-10-yl)-4,6-dimethyl-3-oxo-3H-phenoxazine-1,9-dicarboxamide (actinomycin D), (2R,3S,4S)-2-[(4-methoxyphenyl)methyl]-3,4-pyrrolidinediol 3-acetate (anisomycin), 4-[2-(3,5-dimethyl-2-oxo-cyclohexyl)-2-hydroxyethyl]-2,6-piperidinedione (cycloheximide), N-[2-[[[3-(4-chlorophenyl)-2-propenyl]methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulphonamide (KN93), N -[(phenylmethoxy)carbonyl]-L-leucyl-N-[(1S)-1-formyl-3-methylbutyl]-L-leucinamide (MG132), 1,4-ciamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126), (1S,6bR,9aS,11R,11bR) 11-(acetyloxy)-1,6b,7,8,9a,10,11,11b-octahydro-1-(methoxymethyl)-9a,11b-dimethyl-3H-furo[4,3,2-de]indeno[4,5,-h]-2-h]-2-benzopyran-3,6,9-trione (wortmannin) and (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone (rapamycin), 2,3-Dihydro- N,N -dimethyl-2-oxo-3-[(4,5,6,7-tetrahydro-1 H -indol-2-yl)methylene]-1 H -indole-5-sulfonamide (SU6656) were purchased from Tocris (Bio-Techne Corporation).

Techniques:

Journal: The Journal of Biological Chemistry

Article Title: Striatal mGlu 5 -mediated synaptic plasticity is independently regulated by location-specific receptor pools and divergent signaling pathways

doi: 10.1016/j.jbc.2023.104949

Figure Lengend Snippet: Striatal Quis-LTD is sensitive to anisomycin but not rapamycin . Quis-LTD was induced by 15 min administration of Quis ( open bar ). CNQX, APV, and CPCCOEt were administered 5 min prior to Quis for 20 min ( bar is not shown). A , Quis induces LTD in slices from WT ( open circles ) but not from KO mice ( closed squares ). B–F , effects of various drugs ( black bar ) on Quis-LTD in slices from WT mice. MPEP ( B ), LY53 ( C ), and rapamycin ( F ) were administered 5 min prior to Quis, whereas anisomycin ( D ) was administered 30 min prior to Quis. U0126 ( closed circles , E ) was continuously administered before and during the entire recording versus Quis alone ( open circles , E ). Values represent the mean ± SEM; n = 5 to 6 slices per treatment. LTD, long-term depression; Quis, quisqualate.

Article Snippet: (+)-α-amino-3,5-dioxo-1,2,4-oxadiazolidine-2-propanoic acid, Quis, DHPG, MPEP, CPCCOEt, (±)-4-(4-aminophenyl)-1,2-dihydro-1-methyl-2-propylcarbamoyl-6,7-methylenedioxyphthalazine (SYM2206), d-2-amino-5-phosphonopentanoic acid (APV), CNQX, 2-amino-(N,N)-1-bis(hexadecahydro-6,13-diisopropyl-2,5,9-trimethyl-1,4,7,11,14-pentaoxo-1H-pyrrolo[2,1]-[1,4,7,10,13] oxatetraazacyclohexadecin-10-yl)-4,6-dimethyl-3-oxo-3H-phenoxazine-1,9-dicarboxamide (actinomycin D), (2R,3S,4S)-2-[(4-methoxyphenyl)methyl]-3,4-pyrrolidinediol 3-acetate (anisomycin), 4-[2-(3,5-dimethyl-2-oxo-cyclohexyl)-2-hydroxyethyl]-2,6-piperidinedione (cycloheximide), N-[2-[[[3-(4-chlorophenyl)-2-propenyl]methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulphonamide (KN93), N -[(phenylmethoxy)carbonyl]-L-leucyl-N-[(1S)-1-formyl-3-methylbutyl]-L-leucinamide (MG132), 1,4-ciamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126), (1S,6bR,9aS,11R,11bR) 11-(acetyloxy)-1,6b,7,8,9a,10,11,11b-octahydro-1-(methoxymethyl)-9a,11b-dimethyl-3H-furo[4,3,2-de]indeno[4,5,-h]-2-h]-2-benzopyran-3,6,9-trione (wortmannin) and (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone (rapamycin), 2,3-Dihydro- N,N -dimethyl-2-oxo-3-[(4,5,6,7-tetrahydro-1 H -indol-2-yl)methylene]-1 H -indole-5-sulfonamide (SU6656) were purchased from Tocris (Bio-Techne Corporation).

Techniques:

Journal: The Journal of Neuroscience

Article Title: Activation of Metabotropic Glutamate Receptor 5 Has Direct Excitatory Effects and Potentiates NMDA Receptor Currents in Neurons of the Subthalamic Nucleus

doi: 10.1523/JNEUROSCI.20-21-07871.2000

Figure Lengend Snippet: mGluR5 mediates group I mGluR-evoked depolarization of STN neurons. A, Membrane potential traces showing depolarization with DHPG (100 μm), which is blocked by the mGluR5-selective antagonist MPEP (10 μm). Membrane depolarization is not blocked by the mGluR1-selective antagonist CPCCOEt (100 μm).B, Mean data ± SEM of change in membrane potential showing a significant inhibition of DHPG-mediated depolarization of STN neurons by MPEP (10 μm) compared with DHPG alone (**p < 0.001). MPEP also significantly blocks depolarization mediated by the mGluR5-selective agonist CBPG (100 μm) (*p < 0.05).

Article Snippet: We thank Dr. Carmelo Romano (Washington University) for supplying anti-mGluR1a and anti-mGluR5 antibodies, Dr. Darryle Schoepp and Dr. James Monn (Eli Lilly) for supplying LY354740, Dr. Rainer Kuhn (Novartis) for supplying MPEP and CPCCOEt, and Stephanie Carter for valuable technical assistance.

Techniques: Membrane, Inhibition

Journal: The Journal of Neuroscience

Article Title: Activation of Metabotropic Glutamate Receptor 5 Has Direct Excitatory Effects and Potentiates NMDA Receptor Currents in Neurons of the Subthalamic Nucleus

doi: 10.1523/JNEUROSCI.20-21-07871.2000

Figure Lengend Snippet: mGluR5 mediates group I mGluR-induced potentiation of NMDA-evoked currents. A, Current traces of NMDA-evoked currents before, during, and after application of DHPG (100 μm). The potentiation is blocked by MPEP (10 μm) but not CPCCOEt (100 μm).B, Mean data ± SEM of percent potentiation of NMDA-evoked currents by DHPG over predrug conditions. MPEP (10 μm) significantly blocks potentiation of NMDA-evoked current compared with DHPG alone (*p < 0.05).

Article Snippet: We thank Dr. Carmelo Romano (Washington University) for supplying anti-mGluR1a and anti-mGluR5 antibodies, Dr. Darryle Schoepp and Dr. James Monn (Eli Lilly) for supplying LY354740, Dr. Rainer Kuhn (Novartis) for supplying MPEP and CPCCOEt, and Stephanie Carter for valuable technical assistance.

Techniques:

Journal: The Journal of Neuroscience

Article Title: Synaptic Plasticity in the Amygdala in a Model of Arthritic Pain: Differential Roles of Metabotropic Glutamate Receptors 1 and 5

doi: 10.1523/JNEUROSCI.23-01-00052.2003

Figure Lengend Snippet: Differential changes of mGluR1- and mGluR5-mediated effects in the arthritis pain model. A, In a CeA neuron recorded in a brain slice from a normal rat, MPEP (1 μm; mGluR5 antagonist) inhibited synaptic transmission, whereas CPCCOEt (10 μm; mGluR1 antagonist) had no effect.B, In a CeA neuron from an arthritic rat (6 hr after induction), both CPCCOEt and MPEP inhibited synaptic transmission, suggesting a change in the endogenous activation of mGluR1 in the arthritis pain model. Each trace is the average of 8–10 monosynaptic EPSCs recorded at –60 mV. Drugs were applied by superfusion of the slice in ACSF for at least 10 min. Data shown were recorded at 10–12 min. C, CPCCOEt inhibited synaptic transmission in neurons from arthritic rats (EC50, 94 nm;n = 9) but not in neurons from normal rats (n = 11), suggesting a change in the activation state of mGluR1 in the arthritis pain model.D, Analysis of the raw data (EPSC peak amplitude in picoamperes) shows that blocking of mGluR1 by CPCCOEt significantly reduced the increased EPSC amplitude in CeA neurons from arthritic rats to control levels measured in neurons from nonarthritic rats.E, The inhibitory effects of MPEP on synaptic transmission in CeA neurons were not significantly different in normal rats (EC50, 28.3 nm;n = 10) and in arthritis (EC50, 27.7 nm;n = 9; p> 0.05; two-way ANOVA). F, Analysis of the raw data (picoamperes) shows that MPEP reduced a larger portion of the increased EPSC in arthritis than in control neurons; however, the MPEP-insensitive component of the EPSC also increased in arthritis. ***p < 0.001; unpaired ttest.

Article Snippet: Analysis of the concentration–response relationships showed that CPCCOEt (mGluR1 antagonist) (Fig. C ) inhibited synaptic transmission at the PB→CeA synapse in the arthritis pain model (EC 50 , 94 n m ; n = 9 neurons) (Fig. C , filled circles ), whereas CPCCOEt had no significant effect on synaptic transmission under normal conditions; i.e., the slope of the concentration-response curve was not significantly different from zero ( p > 0.05; F (1,3) = 6.482; n = 11; linear regression analysis, Prism 3.0, GraphPad software) (Fig. C , open circles ).

Techniques: Slice Preparation, Transmission Assay, Activation Assay, Blocking Assay, Control