Abstract
1 Group I metabotropic glutamate receptors (mGluRs) are thought to be important modulators of neuronal function in the superior colliculus (SC). Here, we investigated the pharmacology and signalling mechanisms underlying group I mGluR-mediated inhibition of neuronal excitability and synaptic transmission in the rat SC slice.
2 The group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) potently depressed synaptically evoked excitatory postsynaptic potentials (EPSPs), currents (EPSCs), and action potentials in a dose-dependent manner (IC50: 6.3 muM). This was strongly reduced by the broad-spectrum antagonist (+)alpha-methyl-4-carboxyphenylglycine (MCPG, 1 mM, similar to95% reduction), by the mGluR1 antagonist LY367385 (100 muM, similar to 80% reduction) but not by the mGluR5 antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP, 1 - 100 muM).
3 The putative mGluR5-specific agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG, 500 muM) also inhibited EPSPs. Interestingly, CHPG's actions were not blocked by MPEP, but LY367385 (100 muM) reduced the effect of CHPG by 50%.
4 Inhibition induced by DHPG was independent of phospholipase C (PLC)/protein kinase C pathways, and did not require intact intracellular Ca2+ stores. It was not abolished but enhanced by the GABA(A) antagonist bicuculline (5 muM), suggesting that DHPG's action was not due to facilitated inhibition or changes in neuronal network activity.
5 The K+ channel antagonist 4-aminopyridine (4-AP, 50- 100 muM) converted the inhibitory effect of DHPG into facilitation. Paired-pulse depression was strongly reduced by DHPG, an effect that was also prevented by 4-AP.
6 Our data indicate that group I agonists regulate transmitter release, presumably via an autoreceptor in the SC. This receptor may be involved in adaptation to repetitive stimulation via a non-PLC mediated pathway.
Original language | English |
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Pages (from-to) | 1421-1433 |
Number of pages | 12 |
Journal | British Journal of Pharmacology |
Volume | 140 |
Issue number | 8 |
DOIs | |
Publication status | Published - Dec 2003 |
Keywords
- DHPG
- CHPG
- paired pulse depression
- slice
- presynaptic
- autoreceptor
- short-term plasticity
- PYRAMIDAL NEURONS
- EXCITATORY TRANSMISSION
- SUPERFICIAL LAYERS
- ARACHIDONIC-ACID
- CALCIUM-CHANNELS
- VISUAL RESPONSES
- CA2+ STORES
- CA1 REGION
- HIPPOCAMPUS
- ACTIVATION