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.

Long-Lasting Potentiation of Epileptiform Bursts by Group I mGluRs Is NMDA Receptor Independent

2000 ◽  
Vol 83 (4) ◽  
pp. 2463-2467 ◽  
Author(s):  
Samvel M. Galoyan ◽  
Lisa R. Merlin
Keyword(s):  
Nmda Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Receptor Activation ◽  
Burst Duration ◽  
Transient Increase ◽  
Burst Frequency ◽  
Epileptiform Discharges ◽  
Group I ◽  
Nmda Receptor Activation

In CA3 pyramidal cells of guinea pig hippocampal slices, picrotoxin (50 μM) elicited spontaneous, rhythmically recurring epileptiform bursts 285–435 ms in duration. The addition of (S)-3,5-dihydroxyphenylglycine (DHPG, 50 μM, 90 min application), a selective group I metabotropic glutamate receptor (mGluR) agonist, resulted in a rapid-onset transient increase in burst frequency. This was followed by a slowly progressive increase in burst duration, with bursts reaching 1.5–3.8 s in duration at 90 min of DHPG application. The potentiation of epileptiform burst duration persisted at least 2 h after agonist removal. To determine whether N-methyl-D-aspartate (NMDA) receptor activation participates in the mGluR-induced potentiation of epileptiform bursts, experiments were carried out in the presence ofd-2-amino-5-phosphonovaleric acid (APV, 50–100 μM), an NMDA receptor antagonist. Application of DHPG in the presence of APV resulted in a significantly enhanced transient increase in burst frequency. Nevertheless, when compared with the control described above, there was no significant alteration in the rate of development of the burst prolongation nor its persistence after washout. In other experiments, application of APV in the presence of fully developed mGluR-induced potentiated bursts (after 90 min washout of DHPG) resulted in no significant change in either burst frequency or duration. The data reveal that both induction and maintenance of group I mGluR-mediated potentiation of epileptiform discharges are NMDA receptor-independent processes, suggesting that epileptogenesis, when induced by group I mGluR activation, may occur and be sustained in the absence of NMDA receptor activation.

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.

scholarly journals Differential ability of the dorsal and ventral rat hippocampus to exhibit group I metabotropic glutamate receptor–dependent synaptic and intrinsic plasticity

2017 ◽  
Vol 1 ◽  
pp. 239821281668979 ◽  
Author(s):  
Patrick Tidball ◽  
Hannah V. Burn ◽  
Kai Lun Teh ◽  
Arturas Volianskis ◽  
Graham L. Collingridge ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Longitudinal Axis ◽  
Functional Differentiation ◽  
Rat Hippocampus ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Intrinsic Plasticity

Background: The hippocampus is critically involved in learning and memory processes. Although once considered a relatively homogenous structure, it is now clear that the hippocampus can be divided along its longitudinal axis into functionally distinct domains, responsible for the encoding of different types of memory or behaviour. Although differences in extrinsic connectivity are likely to contribute to this functional differentiation, emerging evidence now suggests that cellular and molecular differences at the level of local hippocampal circuits may also play a role. Methods: In this study, we have used extracellular field potential recordings to compare basal input/output function and group I metabotropic glutamate receptor-dependent forms of synaptic and intrinsic plasticity in area CA1 of slices taken from the dorsal and ventral sectors of the adult rat hippocampus. Results: Using two extracellular electrodes to simultaneously record field EPSPs and population spikes, we show that dorsal and ventral hippocampal slices differ in their basal levels of excitatory synaptic transmission, paired-pulse facilitation, and EPSP-to-Spike coupling. Furthermore, we show that slices taken from the ventral hippocampus have a greater ability than their dorsal counterparts to exhibit long-term depression of synaptic transmission and EPSP-to-Spike potentiation induced by transient application of the group I mGluR agonist ( RS)-3,5-dihydroxyphenylglycine. Conclusions: Together, our results provide further evidence that the information processing properties of local hippocampal circuits differ in the dorsal and ventral hippocampal sectors, and that these differences may in turn contribute to the functional differentiation that exists along the hippocampal longitudinal axis.

Group I mGluR Activation Turns on a Voltage-Gated Inward Current in Hippocampal Pyramidal Cells

2000 ◽  
Vol 83 (5) ◽  
pp. 2844-2853 ◽  
Author(s):  
Shih-Chieh Chuang ◽  
Riccardo Bianchi ◽  
Robert K. S. Wong
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Calcium Currents ◽  
Resting Potential ◽  
Inward Current ◽  
Voltage Gated ◽  
Group I ◽  
Ionic Mechanisms ◽  
Ca3 Pyramidal Cells

A unique property of the group I metabotropic glutamate receptor (mGluR)-induced depolarization in hippocampal cells is that the amplitude of the depolarization is larger when the response is elicited at more depolarized membrane potentials. Our understanding of the conductance mechanism underlying this voltage-dependent response is incomplete. Through the use of current-clamp and single-electrode voltage-clamp recordings in guinea pig hippocampal slices, we examined the group I mGluR-induced depolarization in CA3 pyramidal cells. The group I mGluR agonists ( S)-3-hydroxyphenylglycine and ( S)-3,5-dihydroxyphenylglycine turned on a voltage-gated inward current ( I mGluR(V)), which was pharmacologically distinct from the voltage-gated sodium and calcium currents intrinsic to the cells. I mGluR(V)was a slowly activating, noninactivating current with a threshold at about −75 mV. In addition to the activation of I mGluR(V), group I mGluR stimulation also produced a voltage-independent decrease in the K+conductance. Our results suggest that the depolarization induced by group I mGluR activation is generated by two ionic mechanisms—a heretofore unrecognized voltage-gated inward current ( I mGluR(V)) that is turned on by depolarization and a voltage-insensitive inward current that results from a turn-off of the K+ conductance. The low-threshold and noninactivating properties of I mGluR(V)allow the current to play a significant role in setting the resting potential and firing pattern of CA3 pyramidal cells.

Group I mGluR-Mediated Silent Induction of Long-Lasting Epileptiform Discharges

1999 ◽  
Vol 82 (2) ◽  
pp. 1078-1081 ◽  
Author(s):  
Lisa R. Merlin
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Epileptiform Activity ◽  
Metabotropic Glutamate ◽  
Epileptiform Discharges ◽  
Transient Activation ◽  
Group I ◽  
Induction Process ◽  
Group I Mglurs ◽  
Mglur Antagonist

Picrotoxin, an antagonist of GABAAreceptor-mediated activity, elicited 320- to 475-ms synchronized bursts from the CA3 region of the guinea pig hippocampal slice. The addition of the selective group I metabotropic glutamate receptor (mGluR) agonist ( S)-3,5-dihydroxyphenylglycine (DHPG, 50 μM; 20- to 45-min application) gradually increased the burst duration to 1–4 s; this effect persisted 2–3 h after agonist removal. To determine whether the induction of this long-lasting effect required ongoing synchronized activity during mGluR activation, DHPG application in a second set of experiments took place in the presence of CNQX and ( R,S)-CPP, antagonists of AMPA/kainate and NMDA receptors, respectively. In these experiments, synchronized bursting was silenced during the mGluR agonist application, yet after wash out of the DHPG and the ionotropic glutamate receptor (iGluR) blockers, epileptiform discharges 1–10 s in duration appeared and persisted at least 2 h after wash out of the mGluR agonist. The potentiated bursts were reversibly shortened by application of 500–1,000 μM (+)-α-methyl-4-carboxyphenylglycine (MCPG) or ( S)-4-carboxyphenylglycine (4CPG), agents with group I mGluR antagonist activity. These data suggest that transient activation of group I mGluRs, even during silencing of synchronized epileptiform activity, may have an epileptogenic effect, converting brief interictal-length discharges into persistent seizure-length events. The induction process is iGluR independent, and the maintenance is largely mediated by the action of endogenous glutamate on group I mGluRs, suggesting that autopotentiation of the group I mGluR-mediated response may underlie the epileptogenesis seen here.

Metabotropic Glutamate Receptor-Mediated Depression of the Slow Afterhyperpolarization Is Gated by Tyrosine Phosphatases in Hippocampal CA1 Pyramidal Neurons

2004 ◽  
Vol 92 (5) ◽  
pp. 2811-2819 ◽  
Author(s):  
David R. Ireland ◽  
Diane Guevremont ◽  
Joanna M. Williams ◽  
Wickliffe C. Abraham
Keyword(s):  
Tyrosine Phosphorylation ◽  
Glutamate Receptor ◽  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Specific Inhibitor ◽  
Tyrosine Phosphatases ◽  
Metabotropic Glutamate ◽  
Ca1 Pyramidal Neurons ◽  
Group I

Group I metabotropic glutamate receptor (mGluR) agonists increase the excitability of hippocampal CAl pyramidal neurons via depression of the postspike afterhyperpolarization. In adult rats, this is mediated by both mGluR1 and -5, but the signal transduction processes involved are unknown. In this study, we investigated whether altered levels of tyrosine phosphorylation of proteins are involved in the depression of the slow-duration afterhyperpolarization (sAHP) by the Group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) in CA1 pyramidal neurons of rat hippocampal slices. Preincubation with the tyrosine kinase inhibitors lavendustin A or genistein, or the Src-specific inhibitor 3-(4-chlorophenyl) 1-(1,1-dimethylethyl)-1 H-pyrazolo[3,4-d]pyrimidin-4-amine (PP2), did not inhibit the DHPG-mediated depression of the sAHP. However, preincubation with the tyrosine phosphatase inhibitor orthovanadate reduced the effects of DHPG. This effect of orthovanadate was prevented by simultaneous inhibition of tyrosine kinases with lavendustin A. Selective activation of either mGluR1 or -5 by application of DHPG plus either the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) or the mGluR1 antagonist (S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385) demonstrated that the effect of inhibiting tyrosine phosphatases is not specific to either subtype of mGluR. These results suggest that the depression of the sAHP induced by activation of mGluR1 and -5 is gated by a balance between tyrosine phosphorylation and dephosphorylation.

Group I mGluR Activation Causes Voltage-Dependent and -Independent Ca2+ Rises in Hippocampal Pyramidal Cells

1999 ◽  
Vol 81 (6) ◽  
pp. 2903-2913 ◽  
Author(s):  
Riccardo Bianchi ◽  
Steven R. Young ◽  
Robert K. S. Wong
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Membrane Depolarization ◽  
Membrane Hyperpolarization ◽  
Voltage Gated ◽  
Group I ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Hippocampal Pyramidal Cells

Group I mGluR activation causes voltage-dependent and -independent Ca2+ rises in hippocampal pyramidal cells. Application of the metabotropic glutamate receptor (mGluR) agonist (1 S,3 R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) or the selective group I mGluR agonist ( S)-3,5-dihydroxyphenylglycine (DHPG) depolarized both CA3 and CA1 pyramidal cells in guinea pig hippocampal slices. Simultaneous recordings of voltage and intracellular Ca2+ levels revealed that the depolarization was accompanied by a biphasic elevation of intracellular Ca2+ concentration ([Ca2+]i): a transient calcium rise followed by a delayed, sustained elevation. The transient [Ca2+]i rise was independent of the membrane potential and was blocked when caffeine was added to the perfusing solution. The sustained [Ca2+]i rise appeared when membrane depolarization reached threshold for voltage-gated Ca2+ influx and was suppressed by membrane hyperpolarization. The depolarization was associated with an increased input resistance and persisted when either the transient or sustained [Ca2+]i responses was blocked. mGluR-mediated voltage and [Ca2+]i responses were blocked by (+)-α-methyl-4-carboxyphenylglycine (MCPG) or ( S)-4-carboxy-3-hydroxyphenylglycine (4C3HPG). These data suggest that in both CA3 and CA1 hippocampal cells, activation of group I mGluRs produced a biphasic accumulation of [Ca2+]i via two paths: a transient release from intracellular stores, and subsequently, by influx through voltage-gated Ca2+ channels. The concurrent mGluR-induced membrane depolarization was not caused by the [Ca2+]i rise.

Sign in / Sign up

Export Citation Format

Share Document