Activation of metabotropic glutamate receptors in conjunction with postsynaptic depolarization triggers a long-term depression of the N-methyl-D-aspartate receptor-mediated synaptic potential in the rat hippocampus

Po-Wu Gean, Fang Chia Chang, Pei Lu Yi, Jju Home Lin, Jing Jane Tsai

Research output: Contribution to journalArticle

Abstract

The mechanism responsible for long-term depression (LTD) of pharmacologically isolated N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic potential (EPSPNMDA) was studied. Intracellular recordings were made from CA1 cells of rat hippocampal slices in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (10 μM) and picrotoxin (50 μM), which block non-NMDA and GABAA receptors, respectively. Intracellular injections of depolarizing pulses (500 ms, 0.3-0.7 nA) at 1 Hz for 5 min in the absence of synaptic stimulation caused a persistent increase in the amplitude of EPSPNMDA. However, coupling postsynaptic depolarization with synaptic activity induced LTD. The EPSPNMDA LTD could be blocked by L-2-amino-3-phosphonopropionic acid (50 μM) or (RS)-α-methyl-4-carboxyphenylglycine (200 μM), specific antagonists for metabotropic glutamate receptors (mGluR). Furthermore, application of trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD, 50 μM), a specific mGluR agonist, in conjunction with postsynaptic depolarizing elicited LTD. In contrast, the mGluR agonists quisqualate or t-ACPD when given alone produced a sustained enhancement of EPSPNMDA. Finally, coupled depolarization did not evoke LTD in slices pretreated with the protein kinase C (PKC) inhibitor calphostin c (60 n M). The present results demonstrate that activation of mGluR is necessary for the induction of LTD of EPSPNMDA and suggest that NMDA receptors are subject to bidirectional regulation by mGluR. Furthermore, the induction of LTD is likely to involve the stimulation of PKC.

Original languageEnglish
Pages (from-to)166-173
Number of pages8
JournalJournal of biomedical science
Volume2
Issue number2
DOIs
Publication statusPublished - 1995 Apr 1

Fingerprint

Synaptic Potentials
Metabotropic Glutamate Receptors
Depolarization
N-Methyl-D-Aspartate Receptors
Rats
Hippocampus
Chemical activation
Excitatory Amino Acid Agonists
Protein Kinase C
Quisqualic Acid
6-Cyano-7-nitroquinoxaline-2,3-dione
D-Aspartic Acid
Picrotoxin
Protein C Inhibitor
Excitatory Postsynaptic Potentials
GABA-A Receptors
Protein Kinase Inhibitors
Cells
Injections
1-amino-1,3-dicarboxycyclopentane

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

Cite this

@article{0490cfc4d32f4b55ad7342a52adf952d,
title = "Activation of metabotropic glutamate receptors in conjunction with postsynaptic depolarization triggers a long-term depression of the N-methyl-D-aspartate receptor-mediated synaptic potential in the rat hippocampus",
abstract = "The mechanism responsible for long-term depression (LTD) of pharmacologically isolated N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic potential (EPSPNMDA) was studied. Intracellular recordings were made from CA1 cells of rat hippocampal slices in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (10 μM) and picrotoxin (50 μM), which block non-NMDA and GABAA receptors, respectively. Intracellular injections of depolarizing pulses (500 ms, 0.3-0.7 nA) at 1 Hz for 5 min in the absence of synaptic stimulation caused a persistent increase in the amplitude of EPSPNMDA. However, coupling postsynaptic depolarization with synaptic activity induced LTD. The EPSPNMDA LTD could be blocked by L-2-amino-3-phosphonopropionic acid (50 μM) or (RS)-α-methyl-4-carboxyphenylglycine (200 μM), specific antagonists for metabotropic glutamate receptors (mGluR). Furthermore, application of trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD, 50 μM), a specific mGluR agonist, in conjunction with postsynaptic depolarizing elicited LTD. In contrast, the mGluR agonists quisqualate or t-ACPD when given alone produced a sustained enhancement of EPSPNMDA. Finally, coupled depolarization did not evoke LTD in slices pretreated with the protein kinase C (PKC) inhibitor calphostin c (60 n M). The present results demonstrate that activation of mGluR is necessary for the induction of LTD of EPSPNMDA and suggest that NMDA receptors are subject to bidirectional regulation by mGluR. Furthermore, the induction of LTD is likely to involve the stimulation of PKC.",
author = "Po-Wu Gean and Chang, {Fang Chia} and Yi, {Pei Lu} and Lin, {Jju Home} and Tsai, {Jing Jane}",
year = "1995",
month = "4",
day = "1",
doi = "10.1007/BF02253068",
language = "English",
volume = "2",
pages = "166--173",
journal = "Journal of Biomedical Science",
issn = "1021-7770",
publisher = "BioMed Central",
number = "2",

}

TY - JOUR

T1 - Activation of metabotropic glutamate receptors in conjunction with postsynaptic depolarization triggers a long-term depression of the N-methyl-D-aspartate receptor-mediated synaptic potential in the rat hippocampus

AU - Gean, Po-Wu

AU - Chang, Fang Chia

AU - Yi, Pei Lu

AU - Lin, Jju Home

AU - Tsai, Jing Jane

PY - 1995/4/1

Y1 - 1995/4/1

N2 - The mechanism responsible for long-term depression (LTD) of pharmacologically isolated N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic potential (EPSPNMDA) was studied. Intracellular recordings were made from CA1 cells of rat hippocampal slices in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (10 μM) and picrotoxin (50 μM), which block non-NMDA and GABAA receptors, respectively. Intracellular injections of depolarizing pulses (500 ms, 0.3-0.7 nA) at 1 Hz for 5 min in the absence of synaptic stimulation caused a persistent increase in the amplitude of EPSPNMDA. However, coupling postsynaptic depolarization with synaptic activity induced LTD. The EPSPNMDA LTD could be blocked by L-2-amino-3-phosphonopropionic acid (50 μM) or (RS)-α-methyl-4-carboxyphenylglycine (200 μM), specific antagonists for metabotropic glutamate receptors (mGluR). Furthermore, application of trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD, 50 μM), a specific mGluR agonist, in conjunction with postsynaptic depolarizing elicited LTD. In contrast, the mGluR agonists quisqualate or t-ACPD when given alone produced a sustained enhancement of EPSPNMDA. Finally, coupled depolarization did not evoke LTD in slices pretreated with the protein kinase C (PKC) inhibitor calphostin c (60 n M). The present results demonstrate that activation of mGluR is necessary for the induction of LTD of EPSPNMDA and suggest that NMDA receptors are subject to bidirectional regulation by mGluR. Furthermore, the induction of LTD is likely to involve the stimulation of PKC.

AB - The mechanism responsible for long-term depression (LTD) of pharmacologically isolated N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic potential (EPSPNMDA) was studied. Intracellular recordings were made from CA1 cells of rat hippocampal slices in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (10 μM) and picrotoxin (50 μM), which block non-NMDA and GABAA receptors, respectively. Intracellular injections of depolarizing pulses (500 ms, 0.3-0.7 nA) at 1 Hz for 5 min in the absence of synaptic stimulation caused a persistent increase in the amplitude of EPSPNMDA. However, coupling postsynaptic depolarization with synaptic activity induced LTD. The EPSPNMDA LTD could be blocked by L-2-amino-3-phosphonopropionic acid (50 μM) or (RS)-α-methyl-4-carboxyphenylglycine (200 μM), specific antagonists for metabotropic glutamate receptors (mGluR). Furthermore, application of trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD, 50 μM), a specific mGluR agonist, in conjunction with postsynaptic depolarizing elicited LTD. In contrast, the mGluR agonists quisqualate or t-ACPD when given alone produced a sustained enhancement of EPSPNMDA. Finally, coupled depolarization did not evoke LTD in slices pretreated with the protein kinase C (PKC) inhibitor calphostin c (60 n M). The present results demonstrate that activation of mGluR is necessary for the induction of LTD of EPSPNMDA and suggest that NMDA receptors are subject to bidirectional regulation by mGluR. Furthermore, the induction of LTD is likely to involve the stimulation of PKC.

UR - http://www.scopus.com/inward/record.url?scp=0028968404&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028968404&partnerID=8YFLogxK

U2 - 10.1007/BF02253068

DO - 10.1007/BF02253068

M3 - Article

VL - 2

SP - 166

EP - 173

JO - Journal of Biomedical Science

JF - Journal of Biomedical Science

SN - 1021-7770

IS - 2

ER -