Reduction of Excitatory Postsynaptic Responses by Persistently Active Metabotropic Glutamate Receptors in the Hippocampus

2003 ◽  
Vol 89 (4) ◽  
pp. 1910-1919 ◽  
Author(s):  
Attila Losonczy ◽  
Peter Somogyi ◽  
Zoltan Nusser
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Synaptic Cleft ◽  
Cell Types ◽  
Receptor Activation ◽  
Presynaptic Receptors ◽  
Relative Increase ◽  
Gabaergic Interneuron ◽  
Metabotropic Glutamate ◽  
Axon Terminals

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 μM (αS)-α-amino-α-[(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 μM L(+)-2-amino-4-phosphonobutyric acid (L-AP4): mGluR4/8; 600 μM L-AP4: mGluR4/7/8; 1 μM (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (DCG-IU): mGluR2/3] and an antagonist (0.2 μM LY341495: mGluR2/3/8) suggests that persistently active mGluR2/3/8 control the excitability of hippocampal network.

scholarly journals Modulation of Pineal Melatonin Synthesis by Glutamate Involves Paracrine Interactions between Pinealocytes and Astrocytes through NF-κB Activation

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Darine Villela ◽  
Victoria Fairbanks Atherino ◽  
Larissa de Sá Lima ◽  
Anderson Augusto Moutinho ◽  
Fernanda Gaspar do Amaral ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Calcium Content ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Metabotropic Glutamate ◽  
Melatonin Synthesis ◽  
Group I ◽  
Glutamatergic Signaling

The glutamatergic modulation of melatonin synthesis is well known, along with the importance of astrocytes in mediating glutamatergic signaling in the central nervous system. Pinealocytes and astrocytes are the main cell types in the pineal gland. The objective of this work was to investigate the interactions between astrocytes and pinealocytes as a part of the glutamate inhibitory effect on melatonin synthesis. Rat pinealocytes isolated or in coculture with astrocytes were incubated with glutamate in the presence of norepinephrine, and the melatonin content, was quantified. The expression of glutamate receptors, the intracellular calcium content and the NF-κB activation were analyzed in astrocytes and pinealocytes. TNF-α's possible mediation of the effect of glutamate was also investigated. The results showed that glutamate's inhibitory effect on melatonin synthesis involves interactions between astrocytes and pinealocytes, possibly through the release of TNF-α. Moreover, the activation of the astrocytic NF-κB seems to be a necessary step. In astrocytes and pinealocytes, AMPA, NMDA, and group I metabotropic glutamate receptors were observed, as well as the intracellular calcium elevation. In conclusion, there is evidence that the modulation of melatonin synthesis by glutamate involves paracrine interactions between pinealocytes and astrocytes through the activation of the astrocytic NF-κB transcription factor and possibly by subsequent TNF-αrelease.

Coexpression of Multiple Metabotropic Glutamate Receptors in Axon Terminals of Single Suprachiasmatic Nucleus Neurons

1998 ◽  
Vol 80 (4) ◽  
pp. 1932-1938 ◽  
Author(s):  
Gong Chen ◽  
Anthony N. van den Pol
Keyword(s):  
Glutamate Receptors ◽  
Suprachiasmatic Nucleus ◽  
Metabotropic Glutamate Receptors ◽  
Single Neuron ◽  
Gaba Release ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Axon Terminals ◽  
Group I ◽  
Second Messenger Pathways

Chen, Gong and Anthony N. van den Pol. Coexpression of multiple metabotropic glutamate receptors in axon terminals of single suprachiasmatic nucleus neurons. J. Neurophysiol. 80: 1932–1938, 1998. Glutamate is the primary excitatory transmitter in axons innervating the hypothalamic suprachiasmatic nucleus (SCN) and is responsible for light-induced phase shifts of circadian rhythms generated by the SCN. By using self-innervating single neuron cultures and patch-clamp electrophysiology, we studied metabotropic glutamate receptors (mGluRs) expressed by SCN neurons. The selective agonists for group I (3,5-dihydroxy-phenylglycine), group II ((S)-4-carboxy-3-hydroxyphenylglycine), and group III (l(+)-2-amino-4-phosphonobutyric acid) mGluRs all depressed the evoked IPSC in a subset (33%) of single autaptic neurons, suggesting a coexpression of all three groups of mGluRs in the same axon terminals of a single neuron. Other neurons showed a variety of combinations of mGluRs, including an expression of only one group of mGluR (18%) or coexpression of two groups of mGluRs (27%). Some neurons had no response to any of the three agonists (22%). The three mGluR agonists had no effect on postsynaptic γ-aminobutyric acid (GABA) receptor responses, indicating a presynaptic modulation of GABA release by mGluRs. We conclude that multiple mGluRs that act through different second messenger pathways are coexpressed in single axon terminals of SCN neurons where they modulate the release of GABA presynaptically, usually inhibiting release.

Intracellular Ca2+ release mediated by metabotropic glutamate receptor activation in the leech giant glial cell.

1997 ◽  
Vol 200 (19) ◽  
pp. 2565-2573
Author(s):  
C Lohr ◽  
J W Deitmer
Keyword(s):  
Membrane Potential ◽  
Glutamate Receptors ◽  
Glutamate Receptor ◽  
Glial Cells ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Cyclopiazonic Acid ◽  
Receptor Activation ◽  
Atpase Inhibitor ◽  
Metabotropic Glutamate

We have investigated the effects of glutamate and glutamate receptor ligands on the intracellular free Ca2+ concentration ([Ca2+]i) and the membrane potential (Em) of single, identified neuropile glial cells in the central nervous system of the leech Hirudo medicinalis. Exposed glial cells of isolated ganglia were filled iontophoretically with the Ca2+ indicator dye Fura-2. Application of glutamate (200-500 mumoll-1) caused biphasic membrane potential shifts and increases in [Ca2+]i, which were only partly reduced by either removing extracellular Ca2+ or blocking ionotropic glutamate receptors with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 50-100 mumol l-1. Metabotropic glutamate receptor (mGluR) ligands had the following rank of potency in inducing a rise in [Ca2+]i: quisqualate (QQ, 200 mumol l-1) > glutamate (200 mumol l-1) > L(+)2-amino-3-phosphonopropionic acid (L-AP3, 200 mumol l-1 > trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD, 400 mumol l-1). The mGluR-selective antagonist (RS)-alpha-methyl-4-carboxyphenylglycine [(RS)-MCPG, 1 mmol l-1] significantly reduced glutamate-evoked increases in [Ca2+]i by 20%. Incubation of the ganglia with the endoplasmic ATPase inhibitor cyclopiazonic acid (CPA, 10 mumol l-1) caused a significant (53%) reduction of glutamate-induced [Ca2+]i transients, while incubation with lithium ions (2 mmol l-1) resulted in a 46% reduction. The effects of depleting the Ca2+ stores with CPA and of CNQX were additive. We conclude that glutamate-induced [Ca2+]i transients were mediated by activation of both Ca(2+)-permeable ionotropic non-NMDA receptors and of metabotropic glutamate receptors leading to Ca2+ release from intracellular Ca2+ stores.

Metabotropic Glutamate Receptor Activation Modulates Sound Level Processing in the Cochlear Nucleus

1998 ◽  
Vol 80 (1) ◽  
pp. 209-217 ◽  
Author(s):  
Dan H. Sanes ◽  
JoAnn McGee ◽  
Edward J. Walsh
Keyword(s):  
Glutamate Receptors ◽  
Glutamate Receptor ◽  
Cochlear Nucleus ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Sound Level ◽  
Metabotropic Glutamate

Sanes, Dan H., JoAnn McGee, and Edward J. Walsh. Metabotropic glutamate receptor activation modulates sound level processing in the cochlear nucleus. J. Neurophysiol. 80: 209–217, 1998. The principal role of ionotropic glutamate receptors in the transmission and processing of information in the auditory pathway has been investigated extensively. In contrast, little is known about the functional contribution of the G-protein–coupled metabotropic glutamate receptors (mGluRs), although their anatomic location suggests that they exercise a significant influence on auditory processing. To investigate this issue, sound-evoked responses were obtained from single auditory neurons in the cochlear nuclear complex of anesthetized cats and gerbils, and metabotropic ligands were administered locally through microionophoretic pipettes. In general, microionophoresis of the mGluR agonists, (1 S,3 R)-1-aminocyclopentane-1,3-dicarboxylic acid or (2 S,1′ S,2′ S)-2-(carboxycyclopropyl)glycine, initially produced a gradual increase in spontaneous and sound-evoked discharge rates. However, activation and recovery times were significantly longer than those observed for ionotropic agonists, such as N-methyl-d-aspartate or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, consistent with the recruitment of a second-messenger system. The efficacy of mGluR agonists was diminished after administration of the mGluR antagonist, (+)-α-methyl-4-carboxyphenylglycine, consistent with a selective action at metabotropic recognition sites. In contrast, two distinct changes were observed after the mGluR agonist had been discontinued for several minutes. Approximately 50% of neurons exhibited a chronic depression of sound-evoked discharge rate reminiscent of long-term depression, a cellular property observed in other systems. Approximately 30% of neurons exhibited a long-lasting enhancement of the sound-evoked response similar to the cellular phenomenon of long-term potentiation. These findings suggest that mGluR activation has a profound influence on the gain of primary afferent driven activity in the caudal cochlear nucleus.

Slow Synaptic Inhibition Mediated by Metabotropic Glutamate Receptor Activation of GIRK Channels

2000 ◽  
Vol 84 (5) ◽  
pp. 2284-2290 ◽  
Author(s):  
Patrick Dutar ◽  
Jeffrey J. Petrozzino ◽  
Huan M. Vu ◽  
Marc F. Schmidt ◽  
David J. Perkel
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Brain Slices ◽  
Vocal Learning ◽  
Receptor Activation ◽  
Synaptic Inhibition ◽  
Postsynaptic Inhibition ◽  
Girk Channels ◽  
Metabotropic Glutamate

Glutamate is the predominant excitatory neurotransmitter in the vertebrate CNS. Ionotropic glutamate receptors mediate fast excitatory actions whereas metabotropic glutamate receptors (mGluRs) mediate a variety of slower effects. For example, mGluRs can mediate presynaptic inhibition, postsynaptic excitation, or, more rarely, postsynaptic inhibition. We previously described an unusually slow form of postsynaptic inhibition in one class of projection neuron in the song-control nucleus HVc of the songbird forebrain. These neurons, which participate in a circuit that is essential for vocal learning, exhibit an inhibitory postsynaptic potential (IPSP) that lasts several seconds. Only a portion of this slow IPSP is mediated by GABAB receptors. Since these cells are strongly hyperpolarized by agonists of mGluRs, we used intracellular recording from brain slices to investigate the mechanism of this hyperpolarization and to determine whether mGluRs contribute to the slow synaptic inhibition. We report that mGluRs hyperpolarize these HVc neurons by activating G protein–coupled, inwardly-rectifying potassium (GIRK) channels. MGluR antagonists blocked this response and the slow synaptic inhibition. Thus, glutamate can combine with GABA to mediate slow synaptic inhibition by activating GIRK channels in the CNS.

Hippocampal Astrocytes In Situ Exhibit Calcium Oscillations That Occur Independent of Neuronal Activity

2002 ◽  
Vol 87 (1) ◽  
pp. 528-537 ◽  
Author(s):  
Wolfgang J. Nett ◽  
Scott H. Oloff ◽  
Ken D. McCarthy
Keyword(s):  
Glutamate Receptors ◽  
Neuronal Activity ◽  
Metabotropic Glutamate Receptors ◽  
Purinergic Receptors ◽  
Receptor Activation ◽  
Calcium Oscillations ◽  
Calcium Wave ◽  
Metabotropic Glutamate ◽  
Hippocampal Astrocytes

Results presented in this study indicate that a large subpopulation (∼65%) of hippocampal astrocytes in situ exhibit calcium oscillations in the absence of neuronal activity. Further, the spontaneous oscillations observed within individual hippocampal astrocytes generally developed asynchronously throughout the astrocyte's fine processes and occasionally spread through a portion of that astrocyte as a calcium wave but do not appear to spread among astrocytes as an intercellular calcium wave. Bath application of cyclopiazonic acid and injection of individual astrocytes with heparin blocked astrocytic calcium oscillations. Application of tetrodotoxin or incubation of slices with bafilomycin A1 had no effect on astrocytic calcium oscillations but did block evoked and spontaneous postsynaptic currents measured in CA1 pyramidal neurons. Application of a cocktail of antagonists for metabotropic glutamate receptors and purinergic receptors had no effect on the astrocytic calcium oscillations but blocked the ability of purinergic and metabotropic glutamatergic agonists to increase astrocytic calcium levels. These results indicate that the spontaneous calcium oscillations observed in hippocampal astrocytes in situ are mediated by IP3 receptor activation, are not dependent on neuronal activity, and do not depend on activation of metabotropic glutamate receptors or purinergic receptors. To our knowledge, this is the first demonstration that astrocytes in situ exhibit intrinsic signaling. This finding supports the hypothesis that astrocytes, independent of neuronal input, may act as pacemakers to modulate neuronal activity in situ.

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