DOI: 10.1152/jn.2002.88.4.1625. Role of Synaptic Metabotropic Glutamate Receptors in Epileptiform Discharges in Hippocampal Slices

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

10.1152/jn.2002.88.4.1625

Crossref journal-article

American Physiological Society

Journal of Neurophysiology (24)

Abstract

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.

Bibliography

Lee, A. C., Wong, R. K. S., Chuang, S.-C., Shin, H.-S., & Bianchi, R. (2002). Role of Synaptic Metabotropic Glutamate Receptors in Epileptiform Discharges in Hippocampal Slices. Journal of Neurophysiology, 88(4), 1625â1633.

Authors 5

Angela C. Lee (first)
Robert K. S. Wong (additional)
Shih-Chieh Chuang (additional)
Hee-Sup Shin (additional)
Riccardo Bianchi (additional)

References 53 Referenced 43

10.1016/S0165-0173(98)00050-2
10.1016/0006-8993(94)01243-B
10.1016/S0006-8993(98)00698-2
10.1113/jphysiol.1995.sp020908
10.1093/jnen/59.1.1
10.1016/S0959-4388(99)80044-0
10.1515/REVNEURO.2001.12.2.121
10.1016/S0304-3940(99)00341-9
10.1113/jphysiol.1982.sp014180
10.1002/(SICI)1097-4547(19980201)51:3<339::AID-JNR7>3.0.CO;2-H
10.1016/S0028-3908(99)00242-7
10.1016/S0014-2999(99)00014-X
10.1523/JNEUROSCI.21-16-06387.2001
10.1113/jphysiol.2001.013309
10.1016/S0960-894X(97)10071-3
10.1146/annurev.pharmtox.37.1.205
10.1038/228676a0
10.1016/S0022-3565(25)12302-1 / J Pharmacol Exp Ther by Dalby NO (1996)
10.1016/S0165-6147(00)01635-7
{'key': 'B20', 'first-page': '3', 'volume': '79', 'author': 'Delgado-Escueta AV', 'year': '1999', 'journal-title': 'Adv Neurol'} / Adv Neurol by Delgado-Escueta AV (1999)
10.1046/j.1460-9568.1999.00549.x
10.1113/jphysiol.1992.sp018932
10.1016/S0022-3565(24)38321-1 / J Pharmacol Exp Ther by Gasparini F (1999)
10.1016/S0028-3908(99)00082-9
10.1038/15996
10.1152/jn.1996.76.4.2808
10.1016/S0304-3940(97)00508-9
10.1007/BF00255246
10.1007/s004240050915
10.1038/38508
10.1152/jn.2001.86.6.2878
10.1146/annurev.physiol.63.1.815
10.1152/jn.00579.2001
10.1152/jn.1995.74.2.896
10.1152/jn.1997.78.1.539
10.1016/0306-4522(84)90012-5
10.1523/JNEUROSCI.20-05-01831.2000
10.1152/jn.1991.65.4.771
10.1146/annurev.ne.01.030178.002143
10.1152/jn.1999.81.1.288
10.1152/jn.1987.57.6.1911
10.1007/BF00247601
10.1016/0006-8993(91)90751-G
10.1113/jphysiol.1987.sp016517
10.1038/336379a0
10.1523/JNEUROSCI.15-12-08039.1995
10.1016/0028-3908(95)00083-I
10.1152/jn.2001.85.6.2490
10.1126/science.7079735
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{'key': 'B51', 'first-page': '583', 'volume': '44', 'author': 'Wong RKS', 'year': '1986', 'journal-title': 'Adv Neurol'} / Adv Neurol by Wong RKS (1986)
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Dates

Type	When
Created	7 years, 8 months ago (Dec. 21, 2017, 4:14 p.m.)
Deposited	2 months, 1 week ago (June 28, 2025, 11:49 p.m.)
Indexed	2 months, 1 week ago (June 29, 2025, 12:10 a.m.)
Issued	22 years, 11 months ago (Oct. 1, 2002)
Published	22 years, 11 months ago (Oct. 1, 2002)
Published Print	22 years, 11 months ago (Oct. 1, 2002)

Funders 0

None

BibTeX

@article{Lee_2002, title={Role of Synaptic Metabotropic Glutamate Receptors in Epileptiform Discharges in Hippocampal Slices}, volume={88}, ISSN={1522-1598}, url={http://dx.doi.org/10.1152/jn.2002.88.4.1625}, DOI={10.1152/jn.2002.88.4.1625}, number={4}, journal={Journal of Neurophysiology}, publisher={American Physiological Society}, author={Lee, Angela C. and Wong, Robert K. S. and Chuang, Shih-Chieh and Shin, Hee-Sup and Bianchi, Riccardo}, year={2002}, month=oct, pages={1625–1633} }

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