scholarly journals The Density of Group I mGlu5 Receptors Is Reduced along the Neuronal Surface of Hippocampal Cells in a Mouse Model of Alzheimer’s Disease

2021 ◽  
Vol 22 (11) ◽  
pp. 5867
Author(s):  
Alejandro Martín-Belmonte ◽  
Carolina Aguado ◽  
Rocío Alfaro-Ruiz ◽  
José Luis Albasanz ◽  
Mairena Martín ◽  
...  
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Granule Cells ◽  
Quantitative Description ◽  
Pyramidal Cells ◽  
Receptor Subtype ◽  
Subcellular Localisation ◽  
Principal Cells ◽  
Metabotropic Glutamate ◽  
Model Of Alzheimer’S Disease ◽  
Group I

Metabotropic glutamate receptor subtype 5 (mGlu5) is implicated in the pathophysiology of Alzheimer´s disease (AD). However, its alteration at the subcellular level in neurons is still unexplored. Here, we provide a quantitative description on the expression and localisation patterns of mGlu5 in the APP/PS1 model of AD at 12 months of age, combining immunoblots, histoblots and high-resolution immunoelectron microscopic approaches. Immunoblots revealed that the total amount of mGlu5 protein in the hippocampus, in addition to downstream molecules, i.e., Gq/11 and PLCβ1, was similar in both APP/PS1 mice and age-matched wild type mice. Histoblots revealed that mGlu5 expression in the brain and its laminar expression in the hippocampus was also unaltered. However, the ultrastructural techniques of SDS-FRL and pre-embedding immunogold demonstrated that the subcellular localisation of mGlu5 was significantly reduced along the neuronal surface of hippocampal principal cells, including CA1 pyramidal cells and DG granule cells, in APP/PS1 mice at 12 months of age. The decrease in the surface localisation of mGlu5 was accompanied by an increase in its frequency at intracellular sites in the two neuronal populations. Together, these data demonstrate, for the first time, a loss of mGlu5 at the plasma membrane and accumulation at intracellular sites in different principal cells of the hippocampus in APP/PS1 mice, suggesting an alteration of the excitability and synaptic transmission that could contribute to the cognitive dysfunctions in this AD animal model. Further studies are required to elucidate the specificity of mGlu5-associated molecules and downstream signalling pathways in the progression of the pathology.

Requirement of Protein Synthesis for Group I mGluR-Mediated Induction of Epileptiform Discharges

1998 ◽  
Vol 80 (2) ◽  
pp. 989-993 ◽  
Author(s):  
Lisa R. Merlin ◽  
Peter J. Bergold ◽  
Robert K. S. Wong
Keyword(s):  
Protein Synthesis ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Progressive Increase ◽  
Protein Synthesis Inhibitors ◽  
Burst Frequency ◽  
Metabotropic Glutamate ◽  
Epileptiform Discharges ◽  
Group I

Merlin, Lisa R., Peter J. Bergold, and Robert K. S. Wong. Requirement of protein synthesis for group I mGluR-mediated induction of epileptiform discharges. J. Neurophysiol. 80: 989–993, 1998. Picrotoxin (50 μM) elicited rhythmic synchronized bursting in CA3 pyramidal cells in guinea pig hippocampal slices. Addition of the selective group I metabotropic glutamate receptor (mGluR) agonist ( S)-3,5-dihydroxyphenylglycine (25 μM) elicited an increase in burst frequency. This was soon followed by a slowly progressive increase in burst duration (BD), converting the brief 250–520 ms picrotoxin-induced synchronized bursts into prolonged discharges of 1–5 s in duration. BD was significantly increased within 60 min and reached a maximum after 2–2.5 h of agonist exposure. The protein synthesis inhibitors anisomycin (15 μM) or cycloheximide (25 μM) significantly impeded the mGluR-mediated development of the prolonged bursts; 90–120 min of agonist application failed to elicit the expected burst prolongation. By contrast, the mGluR-mediated enhancement of burst frequency progressed unimpeded. Furthermore, protein synthesis inhibitors had no significant effect on the frequency or duration of fully developed mGluR-induced prolonged discharges. These results suggest that the group I mGluR-mediated prolongation of synchronized bursts has a protein synthesis-dependent mechanism.

β-NAAG Rescues LTP From Blockade by NAAG in Rat Dentate Gyrus via the Type 3 Metabotropic Glutamate Receptor

2001 ◽  
Vol 85 (3) ◽  
pp. 1097-1106 ◽  
Author(s):  
Paul M. Lea IV ◽  
Barbara Wroblewska ◽  
John M. Sarvey ◽  
Joseph H. Neale
Keyword(s):  
Dentate Gyrus ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Granule Cells ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group Ii ◽  
Type 3 ◽  
Mglur Antagonist ◽  
In Cells

N-Acetylaspartylglutamate (NAAG) is an agonist at the type 3 metabotropic glutamate receptor (mGluR3), which is coupled to a Gi/o protein. When activated, the mGluR3 receptor inhibits adenylyl cyclase and reduces the cAMP-mediated second-messenger cascade. Long-term potentiation (LTP) in the medial perforant path (MPP) of the hippocampal dentate gyrus requires increases in cAMP. The presence of mGluR3 receptors and NAAG in neurons of the dentate gyrus suggests that this peptide transmitter may inhibit LTP in the dentate gyrus. High-frequency stimulation (100 Hz; 2 s) of the MPP resulted in LTP of extracellularly recorded excitatory postsynaptic potentials at the MPP-granule cell synapse of rat hippocampal slices. Perfusion of the slice with NAAG (50 and 200 μM) blocked LTP. Neither 50 nor 200 μM NAAG produced N-methyl-d-aspartate receptor currents in the granule cells of the acute hippocampal slice. The group II mGluR antagonist ethyl glutamate (100 μM) and a structural analogue of NAAG, β-NAAG (100 μM), prevented the blockade of LTP by NAAG. Paired-pulse depression of the excitatory postsynaptic potential at 20- and 80-ms interpulse intervals (IPI) was not affected by NAAG or β-NAAG. β-NAAG did not affect inositol trisphosphate production stimulated by the agonist glutamate in cells expressing the group I mGluR1α or mGluR5. β-NAAG blocked the decrease in forskolin-stimulated cAMP by the group II mGluR agonist (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (DCG-IV) but not the group III mGluR agonist L(+)-2-amino-4-phosphonobutyric acid in cerebellar granule cells. In cells transfected with mGluR3, but not mGluR2, β-NAAG blocked forskolin-stimulated cAMP responses to glutamate, NAAG, the nonspecific group I, II agonist trans-ACPD, and the group II agonist DCG-IV. We conclude that β-NAAG is a selective mGluR antagonist capable of differentiating between mGluR2 and mGluR3 subtypes and that the mGluR3 receptor functions to regulate activity-dependent synaptic potentiation in the hippocampus.

Role of Metabotropic Glutamate Receptor Subtype mGluR1 in Brief Nociception and Central Sensitization of Primate STT Cells

1999 ◽  
Vol 82 (1) ◽  
pp. 272-282 ◽  
Author(s):  
Volker Neugebauer ◽  
Ping-Sun Chen ◽  
William D. Willis
Keyword(s):  
Dorsal Horn ◽  
Central Sensitization ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Subtype ◽  
Spinothalamic Tract ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group I Mglurs

G-protein coupled metabotropic glutamate receptors (mGluRs) are important modulators of synaptic transmission in the mammalian CNS and have been implicated in various forms of neuroplasticity and nervous system disorders. Increasing evidence also suggests an involvement of mGluRs in nociception and pain behavior although the contribution of individual mGluR subtypes is not yet clear. Subtypes mGluR1 and mGluR5 are classified as group I mGluRs and share the ability to stimulate phosphoinositide hydrolysis and activate protein kinase C. The present study examined the role of group I mGluRs in nociceptive processing and capsaicin-induced central sensitization of primate spinothalamic tract (STT) cells in vivo. In 10 anesthetized male monkeys ( Macaca fascicularis) extracellular recordings were made from 20 STT cells in the lumbar dorsal horn. Responses to brief (15 s) cutaneous stimuli of innocuous (BRUSH) and barely and substantially noxious (PRESS and PINCH, respectively) intensity were recorded before, during, and after the infusion of group I mGluR agonists and antagonists into the dorsal horn by microdialysis. Cumulative concentration–response relationships were obtained by applying different concentrations for at least 20 min each (at 5 μl/min). The actual concentrations reached in the tissue are 2–3 orders of magnitude lower than those in the microdialysis fibers (values in this paper refer to the latter). The group I antagonists were also applied at 10–25 min after capsaicin injection. S-DHPG, a group I agonist at both mGluR1 and mGluR5, potentiated the responses to innocuous and noxious stimuli (BRUSH > PRESS > PINCH) at low concentrations (10–100 μM; n = 5) but had inhibitory effects at higher concentrations (1–10 mM; n = 5). The mGluR5 agonist CHPG (1 μM-100 mM; n = 5) did not potentiate but inhibited all responses (10–100 mM; n = 5). AIDA (1 μM-100 mM), a mGluR1-selective antagonist, dose-dependently depressed the responses to PINCH and PRESS but not to BRUSH ( n = 6). The group I (mGluR1 > mGluR5) antagonist CPCCOEt (1 μM-100 mM) had similar effects ( n = 6). Intradermal injections of capsaicin sensitized the STT cells to cutaneous mechanical stimuli. The enhancement of the responses by capsaicin resembled the potentiation by the group I mGluR agonist S-DHPG (BRUSH > PRESS > PINCH). CPCCOEt (1 mM) reversed the capsaicin-induced sensitization when given as posttreatment ( n = 5). After washout of CPCCOEt, the sensitization resumed. Similarly, AIDA (1 mM; n = 7) reversed the capsaicin-induced sensitization and also blocked the potentiation by S-DHPG ( n = 5). These data suggest that the mGluR1 subtype is activated endogenously during brief high-intensity cutaneous stimuli (PRESS, PINCH) and is critically involved in capsaicin-induced central sensitization.

scholarly journals Excitation of Cerebellar Interneurons by Group I Metabotropic Glutamate Receptors

2004 ◽  
Vol 92 (3) ◽  
pp. 1558-1565 ◽  
Author(s):  
Movses H. Karakossian ◽  
Thomas S. Otis
Keyword(s):  
Glutamate Receptors ◽  
Glutamate Receptor ◽  
Ampa Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Low Frequency ◽  
Parallel Fiber ◽  
Receptor Subtype ◽  
Metabotropic Glutamate ◽  
Group I

Cerebellar basket and stellate neurons (BSNs) provide feed-forward inhibition to Purkinje neurons (PNs) and thereby play a principal role in determining the output of the cerebellar cortex. During low-frequency transmission, glutamate released at parallel fiber synapses excites BSNs by binding to AMPA receptors; high-frequency transmission also recruits N-methyl-d-aspartate (NMDA) receptors. We find that, in addition to these ligand-gated receptors, a G-protein–coupled glutamate receptor subtype participates in exciting BSNs. Stimulation of metabotropic glutamate receptor 1α (mGluR1α) with the mGluR agonist ( RS)-3,5-dihydroxyphenylglycine (DHPG) leads to an increase in spontaneous firing of BSNs and indirectly to an increase in the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded in PNs. Under conditions in which ligand-gated glutamate receptors are blocked, parallel fiber stimulation generates a slow excitatory postsynaptic current (EPSC) in BSNs that is inhibited by mGluR1α-selective antagonists. This slow EPSC is capable of increasing BSN spiking and indirectly increasing sIPSCs frequency in PNs. Our findings reinforce the idea that distinct subtypes of glutamate receptors are activated in response to different patterns of activity at excitatory synapses. The results also raise the possibility that mGluR1α-dependent forms of synaptic plasticity may occur at excitatory inputs to BSNs.

Characterization with [3H]quisqualate of group I metabotropic glutamate receptor subtype in rat central and peripheral excitable tissues

2001 ◽  
Vol 38 (3) ◽  
pp. 277-285 ◽  
Author(s):  
Eiichi Hinoi ◽  
Kiyokazu Ogita ◽  
Yutaka Takeuchi ◽  
Hiroshi Ohashi ◽  
Takaharu Maruyama ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Subtype ◽  
Metabotropic Glutamate ◽  
Group I

Alcohol Addiction- Metabotropic Glutamate Receptor Subtype 5 and its Ligands: How They All Come Together?

2018 ◽  
Vol 19 (8) ◽  
pp. 907-915 ◽  
Author(s):  
Jaya Kumar ◽  
Zalina Ismail ◽  
Nurul Hazwani Hatta ◽  
Najwa Baharuddin ◽  
Hermizi Hapidin ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Alcohol Addiction ◽  
Receptor Subtype ◽  
Metabotropic Glutamate

Group I Metabotropic Glutamate Receptors Are Differentially Expressed by Two Populations of Olfactory Bulb Granule Cells

2007 ◽  
Vol 97 (4) ◽  
pp. 3136-3141 ◽  
Author(s):  
Thomas Heinbockel ◽  
Kathryn A. Hamilton ◽  
Matthew Ennis
Keyword(s):  
Olfactory Bulb ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Granule Cells ◽  
Mitral Cell ◽  
Mitral Cells ◽  
Patch Clamp Recording ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Bath Application

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.

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