Activation of presynaptic group III metabotropic receptors enhances glutamate release in rat entorhinal cortex

D I Evans, Roland S G Jones, G Woodhall

Research output: Contribution to journalArticle

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Abstract

The role of group III metabotropic glutamate receptors (mGluRs) in modulating excitatory synaptic transmission was investigated in the rat entorhinal cortex (EC) in vitro. AMPA receptor-mediated excitatory postsynaptic currents (EPSCs) were recorded in the whole cell configuration of the patch-clamp technique from visually identified neurons in layers V and II. In layer V, bath application of the specific group III mGluR agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4, 500 mu M) resulted in a marked facilitation of both spontaneous and activity-independent "miniature" (s/ mEPSC) event frequency. Thr facilitatory effect of L-AP4 (100 mu M) on sEPSC frequency prevailed in the presence of DL-2-amino-5-phosphonopentanoic acid (100 mu M) but was abolished by the group III antagonist (RS)-cyclopropyl-4-phosphonophenylglycine (20 mu M). These data confirmed that group III mGluRs, and not N-methyl-D-aspartate (NMDA) receptors were involved in the response to L-AP4. Bath application of the specific mGluR4a agonist (1S,3R,4S)-1-aminocyclopentane-1,2, 4-tricarboxylic acid (20 mu M) also had a facilitatory effect on sEPSC frequency, suggesting involvement of mGluR4a. In layer II neurons, L-AP4 caused a reduction in sEPSC frequency but did not affect mEPSCs recorded in the presence of tetrodotoxin. These findings suggest that a group III mGluR with mGluR4a-like pharmacology is involved in modulating synaptic transmission in layer V cells of the EC. The effect on mEPSCs suggests that this receptor is located presynaptically and that its activation results in a direct facilitation of glutamate release. This novel facilitatory effect is specific to layer V and, to our knowledge, is the first report of a direct facilitatory action of group III mGluRs on synaptic transmission. In layer II, L-AP4 had an inhibitory effect on glutamate release similar to that reported in other brain regions.
Original languageEnglish
Pages (from-to)2519-2525
Number of pages7
JournalJournal of Neurophysiology
Volume83
Issue number5
Publication statusPublished - 2000

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Entorhinal Cortex
Metabotropic Glutamate Receptors
Synaptic Transmission
Baths
Glutamic Acid
2-Amino-5-phosphonovalerate
Neurons
AMPA Receptors
Excitatory Postsynaptic Potentials
Tetrodotoxin
Patch-Clamp Techniques
N-Methyl-D-Aspartate Receptors
2-amino-4-phosphono-propinate
Pharmacology
Brain
2-amino-4-phosphonobutyrate receptor

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Activation of presynaptic group III metabotropic receptors enhances glutamate release in rat entorhinal cortex. / Evans, D I; Jones, Roland S G; Woodhall, G.

In: Journal of Neurophysiology, Vol. 83, No. 5, 2000, p. 2519-2525.

Research output: Contribution to journalArticle

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N2 - The role of group III metabotropic glutamate receptors (mGluRs) in modulating excitatory synaptic transmission was investigated in the rat entorhinal cortex (EC) in vitro. AMPA receptor-mediated excitatory postsynaptic currents (EPSCs) were recorded in the whole cell configuration of the patch-clamp technique from visually identified neurons in layers V and II. In layer V, bath application of the specific group III mGluR agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4, 500 mu M) resulted in a marked facilitation of both spontaneous and activity-independent "miniature" (s/ mEPSC) event frequency. Thr facilitatory effect of L-AP4 (100 mu M) on sEPSC frequency prevailed in the presence of DL-2-amino-5-phosphonopentanoic acid (100 mu M) but was abolished by the group III antagonist (RS)-cyclopropyl-4-phosphonophenylglycine (20 mu M). These data confirmed that group III mGluRs, and not N-methyl-D-aspartate (NMDA) receptors were involved in the response to L-AP4. Bath application of the specific mGluR4a agonist (1S,3R,4S)-1-aminocyclopentane-1,2, 4-tricarboxylic acid (20 mu M) also had a facilitatory effect on sEPSC frequency, suggesting involvement of mGluR4a. In layer II neurons, L-AP4 caused a reduction in sEPSC frequency but did not affect mEPSCs recorded in the presence of tetrodotoxin. These findings suggest that a group III mGluR with mGluR4a-like pharmacology is involved in modulating synaptic transmission in layer V cells of the EC. The effect on mEPSCs suggests that this receptor is located presynaptically and that its activation results in a direct facilitation of glutamate release. This novel facilitatory effect is specific to layer V and, to our knowledge, is the first report of a direct facilitatory action of group III mGluRs on synaptic transmission. In layer II, L-AP4 had an inhibitory effect on glutamate release similar to that reported in other brain regions.

AB - The role of group III metabotropic glutamate receptors (mGluRs) in modulating excitatory synaptic transmission was investigated in the rat entorhinal cortex (EC) in vitro. AMPA receptor-mediated excitatory postsynaptic currents (EPSCs) were recorded in the whole cell configuration of the patch-clamp technique from visually identified neurons in layers V and II. In layer V, bath application of the specific group III mGluR agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4, 500 mu M) resulted in a marked facilitation of both spontaneous and activity-independent "miniature" (s/ mEPSC) event frequency. Thr facilitatory effect of L-AP4 (100 mu M) on sEPSC frequency prevailed in the presence of DL-2-amino-5-phosphonopentanoic acid (100 mu M) but was abolished by the group III antagonist (RS)-cyclopropyl-4-phosphonophenylglycine (20 mu M). These data confirmed that group III mGluRs, and not N-methyl-D-aspartate (NMDA) receptors were involved in the response to L-AP4. Bath application of the specific mGluR4a agonist (1S,3R,4S)-1-aminocyclopentane-1,2, 4-tricarboxylic acid (20 mu M) also had a facilitatory effect on sEPSC frequency, suggesting involvement of mGluR4a. In layer II neurons, L-AP4 caused a reduction in sEPSC frequency but did not affect mEPSCs recorded in the presence of tetrodotoxin. These findings suggest that a group III mGluR with mGluR4a-like pharmacology is involved in modulating synaptic transmission in layer V cells of the EC. The effect on mEPSCs suggests that this receptor is located presynaptically and that its activation results in a direct facilitation of glutamate release. This novel facilitatory effect is specific to layer V and, to our knowledge, is the first report of a direct facilitatory action of group III mGluRs on synaptic transmission. In layer II, L-AP4 had an inhibitory effect on glutamate release similar to that reported in other brain regions.

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JO - Journal of Neurophysiology

JF - Journal of Neurophysiology

SN - 0022-3077

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