Heterogeneity of metabotropic glutamate receptors in the striatum

Electrophysiological evidence

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

In order to investigate the functional role of metabotropic glutamate receptors (mGluRs) in the striatum we performed extracellular and intracellular recordings from a corticostriatal brain slice preparation. The effects of L-2-amino-3-phosphopropionic acid (L-AP3), an antagonist of mGluRs, were studied both on long-term synaptic depression (LTD) and on presynaptic inhibition of excitatory postsynaptic potentials (EPSPs) Induced by different agonists of mGluRs. L-AP3 produced a dose-dependent (3-30 μM) reduction of the LTD evoked in the striatum by the tetanic stimulation of the corticostriatal pathway. In contrast to this action, L-AP3 (10-100 μM) did not significantly affect the presynaptic inhibitory effect of 1-amino-cyclopentyl-trans-dicarboxylic acid (t-ACPD), an agonist of mGluRs, on corticostriatal transmission. Higher concentrations of L-AP3 (0.3-1 mM) reduced by themselves the EPSP amplitude. The inhibitory effect of t-ACPD on the cortically evoked EPSPs was mimicked either by the active stereoisomer 1S,3R-ACPD or by amino-4-phosphonobutyric acid (L-AP4), a glutamate autoreceptor agonist. In some neurons, these inhibitory actions were coupled with membrane depolarizations. The depression of synaptic transmission caused by t-ACPD, 1S,3R-ACPD and L-AP4 was not altered following the induction of LTD. Chronic lithium treatment of the animals (60-120 mg/kg i.p. for 10 days) blocked striatal LTD but not presynaptic inhibition mediated by mGluR agonists. The present findings show that the mechanisms underlying LTD and the presynaptic inhibition induced by different agonists of mGluRs exhibit functional and pharmacological differences. These data suggest heterogeneity of mGluRs in the striatum.

Original languageEnglish
Pages (from-to)1370-1377
Number of pages8
JournalEuropean Journal of Neuroscience
Volume5
Issue number10
DOIs
Publication statusPublished - 1993

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Long-Term Synaptic Depression
Metabotropic Glutamate Receptors
Excitatory Postsynaptic Potentials
Excitatory Amino Acid Agonists
Corpus Striatum
Autoreceptors
Dicarboxylic Acids
Stereoisomerism
Lithium
Synaptic Transmission
1-amino-1,3-dicarboxycyclopentane
2-amino-3-phosphonopropionic acid
Pharmacology
Neurons
Acids
Membranes
Brain

Keywords

  • 1S,3R-ACPD
  • L-AP3
  • L-AP4
  • LTD
  • Metabotropic glutamate receptors
  • Striatum
  • Synaptic transmission
  • tACPD

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Heterogeneity of metabotropic glutamate receptors in the striatum: Electrophysiological evidence",
abstract = "In order to investigate the functional role of metabotropic glutamate receptors (mGluRs) in the striatum we performed extracellular and intracellular recordings from a corticostriatal brain slice preparation. The effects of L-2-amino-3-phosphopropionic acid (L-AP3), an antagonist of mGluRs, were studied both on long-term synaptic depression (LTD) and on presynaptic inhibition of excitatory postsynaptic potentials (EPSPs) Induced by different agonists of mGluRs. L-AP3 produced a dose-dependent (3-30 μM) reduction of the LTD evoked in the striatum by the tetanic stimulation of the corticostriatal pathway. In contrast to this action, L-AP3 (10-100 μM) did not significantly affect the presynaptic inhibitory effect of 1-amino-cyclopentyl-trans-dicarboxylic acid (t-ACPD), an agonist of mGluRs, on corticostriatal transmission. Higher concentrations of L-AP3 (0.3-1 mM) reduced by themselves the EPSP amplitude. The inhibitory effect of t-ACPD on the cortically evoked EPSPs was mimicked either by the active stereoisomer 1S,3R-ACPD or by amino-4-phosphonobutyric acid (L-AP4), a glutamate autoreceptor agonist. In some neurons, these inhibitory actions were coupled with membrane depolarizations. The depression of synaptic transmission caused by t-ACPD, 1S,3R-ACPD and L-AP4 was not altered following the induction of LTD. Chronic lithium treatment of the animals (60-120 mg/kg i.p. for 10 days) blocked striatal LTD but not presynaptic inhibition mediated by mGluR agonists. The present findings show that the mechanisms underlying LTD and the presynaptic inhibition induced by different agonists of mGluRs exhibit functional and pharmacological differences. These data suggest heterogeneity of mGluRs in the striatum.",
keywords = "1S,3R-ACPD, L-AP3, L-AP4, LTD, Metabotropic glutamate receptors, Striatum, Synaptic transmission, tACPD",
author = "P. Calabresi and A. Pisani and Mercuri, {N. B.} and G. Bernardi",
year = "1993",
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T1 - Heterogeneity of metabotropic glutamate receptors in the striatum

T2 - Electrophysiological evidence

AU - Calabresi, P.

AU - Pisani, A.

AU - Mercuri, N. B.

AU - Bernardi, G.

PY - 1993

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N2 - In order to investigate the functional role of metabotropic glutamate receptors (mGluRs) in the striatum we performed extracellular and intracellular recordings from a corticostriatal brain slice preparation. The effects of L-2-amino-3-phosphopropionic acid (L-AP3), an antagonist of mGluRs, were studied both on long-term synaptic depression (LTD) and on presynaptic inhibition of excitatory postsynaptic potentials (EPSPs) Induced by different agonists of mGluRs. L-AP3 produced a dose-dependent (3-30 μM) reduction of the LTD evoked in the striatum by the tetanic stimulation of the corticostriatal pathway. In contrast to this action, L-AP3 (10-100 μM) did not significantly affect the presynaptic inhibitory effect of 1-amino-cyclopentyl-trans-dicarboxylic acid (t-ACPD), an agonist of mGluRs, on corticostriatal transmission. Higher concentrations of L-AP3 (0.3-1 mM) reduced by themselves the EPSP amplitude. The inhibitory effect of t-ACPD on the cortically evoked EPSPs was mimicked either by the active stereoisomer 1S,3R-ACPD or by amino-4-phosphonobutyric acid (L-AP4), a glutamate autoreceptor agonist. In some neurons, these inhibitory actions were coupled with membrane depolarizations. The depression of synaptic transmission caused by t-ACPD, 1S,3R-ACPD and L-AP4 was not altered following the induction of LTD. Chronic lithium treatment of the animals (60-120 mg/kg i.p. for 10 days) blocked striatal LTD but not presynaptic inhibition mediated by mGluR agonists. The present findings show that the mechanisms underlying LTD and the presynaptic inhibition induced by different agonists of mGluRs exhibit functional and pharmacological differences. These data suggest heterogeneity of mGluRs in the striatum.

AB - In order to investigate the functional role of metabotropic glutamate receptors (mGluRs) in the striatum we performed extracellular and intracellular recordings from a corticostriatal brain slice preparation. The effects of L-2-amino-3-phosphopropionic acid (L-AP3), an antagonist of mGluRs, were studied both on long-term synaptic depression (LTD) and on presynaptic inhibition of excitatory postsynaptic potentials (EPSPs) Induced by different agonists of mGluRs. L-AP3 produced a dose-dependent (3-30 μM) reduction of the LTD evoked in the striatum by the tetanic stimulation of the corticostriatal pathway. In contrast to this action, L-AP3 (10-100 μM) did not significantly affect the presynaptic inhibitory effect of 1-amino-cyclopentyl-trans-dicarboxylic acid (t-ACPD), an agonist of mGluRs, on corticostriatal transmission. Higher concentrations of L-AP3 (0.3-1 mM) reduced by themselves the EPSP amplitude. The inhibitory effect of t-ACPD on the cortically evoked EPSPs was mimicked either by the active stereoisomer 1S,3R-ACPD or by amino-4-phosphonobutyric acid (L-AP4), a glutamate autoreceptor agonist. In some neurons, these inhibitory actions were coupled with membrane depolarizations. The depression of synaptic transmission caused by t-ACPD, 1S,3R-ACPD and L-AP4 was not altered following the induction of LTD. Chronic lithium treatment of the animals (60-120 mg/kg i.p. for 10 days) blocked striatal LTD but not presynaptic inhibition mediated by mGluR agonists. The present findings show that the mechanisms underlying LTD and the presynaptic inhibition induced by different agonists of mGluRs exhibit functional and pharmacological differences. These data suggest heterogeneity of mGluRs in the striatum.

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KW - LTD

KW - Metabotropic glutamate receptors

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KW - Synaptic transmission

KW - tACPD

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