Activation of metabotropic glutamate receptors induces long-term depression of GABAergic inhibition in hippocampus

1993 ◽  
Vol 69 (3) ◽  
pp. 1000-1004 ◽  
Author(s):  
Y. B. Liu ◽  
J. F. Disterhoft ◽  
N. T. Slater
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Hippocampal Slices ◽  
Input Resistance ◽  
Nmda Receptor Antagonist ◽  
Metabotropic Glutamate ◽  
Epileptiform Discharges ◽  
Bath Application

1. The long-term enhancement of synaptic excitability in CA1 hippocampal pyramidal neurons produced by activation of metabotropic glutamate receptors (mGluRs) was studied in rabbit hippocampal slices in vitro. 2. Bath application of the mGluR agonist (1S,3R)-1-aminocyclopentane-1,3- dicarboxylic acid (1S,3R-ACPD) (5-20 microM) for 20 min produced a reversible depolarization of membrane potentiatil, blockade of spike accommodation, and increase in input resistance of CA1 neurons. However, a long-lasting increase in synaptic excitability was observed: single stimuli applied to the Schaffer collateral commisural fiber pathway evoked epileptiform discharges in the presence of 1S,3R-ACPD and after the washout of 1S,3R-ACPD, persistent paroxysmal depolarization shifts (PDSs) were evoked by afferent stimulation. A long-lasting enhancement of synaptic excitability was also observed in the presence of the NMDA receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5), which blocked the stimulation-evoked PDS and associated afterdischarges. 3. When biphasic, monosynaptically evoked inhibitory post-synaptic potentials (IPSPs) were recorded in the presence of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10–15 microM) and D-AP5 (20 microM), the bath application of 1S,3R-ACPD produced a significant reduction (approximately 50%) of both components of the IPSP, which persisted after the washout of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Pattern-Specific Synaptic Mechanisms in a Multifunctional Network. II. Intrinsic Modulation by Metabotropic Glutamate Receptors

2006 ◽  
Vol 95 (3) ◽  
pp. 1334-1344 ◽  
Author(s):  
Steven P. Lieske ◽  
Jan-Marino Ramirez
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Activity Patterns ◽  
Nmda Receptor Antagonist ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Respiratory Network ◽  
Bath Application ◽  
A Minor

The in vitro respiratory network contained in the transverse brain stem slice of mice simultaneously generates fast (∼15 min-1) and slow (∼0.5 min-1) rhythmic activities corresponding to fictive eupnea (“normal” breathing) and fictive sighs. We show that these two activity patterns are differentially controlled through the modulatory actions of metabotropic glutamate receptors (mGluRs). Sighs were selectively inhibited by agonists of the group III mGluRs according to a pharmacological profile most consistent with activation of mGluR8. Sighs were also blocked by the supposedly inactive L-isomer of the widely used N-methyl-d-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonopentanoic acid (L-AP5, 5 μM), an effect that was abolished in the presence of group III mGluR antagonists. Excitatory postsynaptic potentials (EPSPs) were recorded in pre-Bötzinger Complex neurons after stimulation of the contralateral ventral respiratory group (VRG); evoked EPSP amplitude was variably reduced after bath application of the group III agonist l-serine- O-phospate (L-SOP), with an average reduction of 15%. Therefore although group III mGluRs do play a role in regulating synapse strength, this seems to be only a minor factor in the regulation of synapses made by midline-crossing axons. Intrinsic modulation of the respiratory central pattern generator by mGluRs appears to be an essential component of the multifunctionality that characterizes this network.

Role of Group I Metabotropic Glutamate Receptors in the Patterning of Epileptiform Activities In Vitro

1997 ◽  
Vol 78 (1) ◽  
pp. 539-544 ◽  
Author(s):  
Lisa R. Merlin ◽  
Robert K. S. Wong
Keyword(s):  
Guinea Pig ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Hippocampal Slices ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group I Mglurs ◽  
Synaptic Responses

Merlin, Lisa R. and Robert K. S. Wong. Role of group I metabotropic glutamate receptors in the patterning of epileptiform activities in vitro. J. Neurophysiol. 78: 539–544, 1997. In guinea pig hippocampal slices, picrotoxin elicited spontaneous epileptiform bursts 300–550 ms in duration. Additional application of ( R,S)-3,5-dihydroxyphenylglycine or ( S)-3-hydroxyphenylglycine, agonists specific for group I metabotropic glutamate receptors(mGluRs), or (1 S,3 R)-1-aminocyclopentane-1,3-dicarboxylicacid, a broad-spectrum mGluR agonist, converted picrotoxin-induced interictal bursts into prolonged discharges measured on the order of seconds. The prolonged discharges induced by selective group I mGluR agonist continued to be produced for hours after agonist removal. The antagonists ( S)-4-carboxyphenylglycine and (+)-α-methyl-4-carboxyphenylglycine had no effect on the duration of picrotoxin-induced interictal bursts. However, after agonist exposure, the persistent prolonged discharges occurring in the absence of agonist were reversibly suppressed by the antagonists, suggesting that the activity is maintained via endogenous activation of group I mGluRs by synaptically released glutamate. Our results suggest that, under some conditions, activation of group I mGluRs produces long-lasting enhancement of synaptic responses, mediated at least in part by autopotentiation of the group I mGluR response itself, which may result in the production of seizure discharges and contribute to epileptogenesis.

Role of Synaptic Metabotropic Glutamate Receptors in Epileptiform Discharges in Hippocampal Slices

2002 ◽  
Vol 88 (4) ◽  
pp. 1625-1633 ◽  
Author(s):  
Angela C. Lee ◽  
Robert K. S. Wong ◽  
Shih-Chieh Chuang ◽  
Hee-Sup Shin ◽  
Riccardo Bianchi
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Brain Slices ◽  
Wild Type ◽  
Metabotropic Glutamate ◽  
Epileptiform Discharges ◽  
Group I ◽  
Group I Mglurs

Application of group I metabotropic glutamate receptor (mGluR) agonists elicits seizure discharges in vivo and prolonged ictal-like activity in in vitro brain slices. In this study we examined 1) if group I mGluRs are activated by synaptically released glutamate during epileptiform discharges induced by convulsants in hippocampal slices and, if so, 2) whether the synaptically activated mGluRs contribute to the pattern of the epileptiform discharges. The GABAAreceptor antagonist bicuculline (50 μM) was applied to induce short synchronized bursts of ∼250 ms in mouse hippocampal slices. Addition of 4-aminopyridine (4-AP; 100 μM) prolonged these bursts to 0.7–2 s. The mGluR1 antagonist ( S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acid (LY 367385; 25–100 μM) and the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP; 10–50 μM), applied separately, significantly reduced the duration of the synchronized discharges. The effects of these antagonists were additive when applied together, suggesting that mGluR1 and mGluR5 exert independent actions on the epileptiform bursts. In phospholipase C β1 (PLCβ1) knockout mice, bicuculline and 4-AP elicited prolonged synchronized discharges of comparable duration as those observed in slices from wild-type littermates. Furthermore, mGluR1 and mGluR5 antagonists reduced the duration of the epileptiform discharges to the same extent as they did in the wild-type preparations. The results suggest that mGluR1 and mGluR5 are activated synaptically during prolonged epileptiform discharges induced by bicuculline and 4-AP. Synaptic activation of these receptors extended the duration of synchronized discharges. In addition, the data indicate that the synaptic effects of the group I mGluRs on the duration of epileptiform discharges were mediated by a PLCβ1-independent mechanism.

Modulation of epileptiform activity by metabotropic glutamate receptors in immature rat neocortex

1995 ◽  
Vol 73 (1) ◽  
pp. 205-217 ◽  
Author(s):  
J. P. Burke ◽  
J. J. Hablitz
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Epileptiform Activity ◽  
Brain Slices ◽  
Small Population ◽  
Cortical Layers ◽  
Metabotropic Glutamate ◽  
Epileptiform Discharges ◽  
Bath Application ◽  
Rat Neocortex

1. Intracellular and extracellular recordings were obtained from neocortical brain slices of immature rats (postnatal days 9-16) maintained in vitro. Spontaneous and evoked epileptiform discharges (termed paroxysmal depolarizing shifts or PDSs) were recorded from upper cortical laminae (layers II-III) after exposure to the gamma-aminobuturic acid-A receptor antagonist, bicuculline methiodide. The effects of mGluR activation on PDS duration, spontaneous frequency, and threshold for evoking a PDS were determined. Putative mGluR agonists and antagonists also were tested. 2. Bath application of the mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (ACPD, 50-200 mM) elicited biphasic, time-dependent effects on evoked and spontaneous epileptiform discharges. At times early in drug wash-in, ACPD increased PDS duration and spontaneous PDS frequency. In > 60% of the slices, the spontaneous PDSs became regular. Subsequently, ACPD reduced PDS duration and increased the stimulus threshold for evoking a PDS, suggesting that the actions of ACPD were dose dependent. 3. Investigation of the concentration-dependence revealed that sustained low ACPD concentrations (5 microM) elicited only facilitatory actions, whereas higher concentrations were suppressive. These observations suggest the activation of different mGluR subtypes, which may be localized differentially at pre- and postsynaptic sites. 4. Bath application of the mGluR agonists, L-2-amino-4-phosphonobutyrate or (2S,3S,4S)-alpha-(carboxycyclopropyl) glycine, produced only suppressive effects on epileptiform activity in the immature neocortex. L-2-amino-3-phosphonopropionate was an ineffective antagonist of ACPD-mediated modulation of epileptiform activity. Application of the putative antagonist, alpha-methyl-4-carboxyphenylglycine (MCPG), failed to antagonize the biphasic actions of ACPD. MCPG had suppressive effects of epileptiform activity, suggesting activation of mGluRs by endogenous agonists. 5. Simultaneous recordings from deeper and upper cortical layers indicated that the initial negativity of both evoked and spontaneous PDSs began in deeper cortical layers under control conditions and in the presence of ACPD. Intracellular records from neurons in deeper layers displayed two distinct patterns of activity during mGluR activation. Most deep layer neurons received a barrage of excitatory postsynaptic potentials before a spontaneous PDS during ACPD application. A small population of neurons depolarized and entered a tonically firing mode, which was interrupted by spontaneous PDSs. Different neuronal populations, possible expressing different mGluR subtypes or coupling mechanisms, may play integral roles in the induction and generation of epileptiform activities. 6. Thapsigargin or dantrolene, agents thought to block release of Ca2+ from intracellular stores, were both applied for periods < or = min.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Group III Metabotropic Glutamate Receptors (mGluRs) Modulate Transmission of Gustatory Inputs in the Brain Stem

2009 ◽  
Vol 102 (1) ◽  
pp. 192-202 ◽  
Author(s):  
Robert M. Hallock ◽  
Christopher J. Martyniuk ◽  
Thomas E. Finger
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Field Potential ◽  
Taste System ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Bath Application ◽  
Afferent Synapse

Glutamate is the principal neurotransmitter at the primary sensory afferent synapse in the medulla for the taste system. At this synapse, glutamate activates N-methyl-d-aspartate (NMDA) and non-NMDA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA] and kainate) ionotropic receptors to effect a response in the second-order neurons. The current experiment is the first to examine the role of metabotropic glutamate receptors (mGluRs) in the transmission of taste information. In an in vitro slice preparation of the primary vagal gustatory nucleus in goldfish, primary gustatory afferent fibers were stimulated electrically, whereas evoked dendritic field potentials were recorded in the sensory layers. Recordings were made before, during, and after bath application of mGluR agonists for various mGluR groups and subtypes. Whereas l-AP4, a group III agonist, reduced the field potential, group I and group II agonists had no effect. Furthermore, the selective mGluR4 agonist ACPT-III and mGluR8 agonist PPG were effective at reducing the field potential, whereas agonists selective for mGluR6 and 7 were not. MAP4, a group III mGluR antagonist, attenuated frequency-dependent depression, indicating that endogenous glutamate binds to presynaptic mGluRs under normal conditions. Furthermore, polymerase chain reaction showed that mRNA for mGluR4 and 8 is expressed in the vagal ganglia, a prerequisite if those receptors are expressed presynaptically in the vagal lobe. Collectively, these experiments indicate that mGluR4 and 8 are presynaptic at the primary gustatory afferent synapse and that their activation inhibits glutamatergic release.

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