Presynaptic group I metabotropic glutamate receptors modulate synaptic transmission in the rat superior colliculus via 4‐AP sensitive K⁺ channels

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 dosedependent manner (IC 50 : 6.3 mM). This was strongly reduced by the broad-spectrum antagonist ( þ )-alpha-methyl-4-carboxyphenylglycine (MCPG, 1 mM, B95% reduction), by the mGluR1 antagonist LY367385 (100 mM, B80% reduction) but not by the mGluR5 antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP, 1 -100 mM). 3 The putative mGluR5-specific agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG, 500 mM) also inhibited EPSPs. Interestingly, CHPG's actions were not blocked by MPEP, but LY367385 (100 mM) 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 Ca 2 þ stores. It was not abolished but enhanced by the GABA A antagonist bicuculline (5 mM), suggesting that DHPG's action was not due to facilitated inhibition or changes in neuronal network activity. 5 The K þ channel antagonist 4-aminopyridine (4-AP, 50 -100 mM) 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.

Driving Cellular Plasticity and Survival Through the Signal Transduction Pathways of Metabotropic Glutamate Receptors

“…In the adult mammalian, electrophysiological studies of mGluRs have shown that activation of mGluRs may lead to a range of cellular changes such as the inhibition of calcium and potassium currents, mediation of slow excitatory postsynaptic potential, and the presynaptic inhibition of transmitter release (Anwyl, R, 1999, Losonczy, A et al, 2003, White, AM et al, 2003. In particular, activation of group I mGluRs can contribute to slow-onset potentiation in the hippocampal region of CA1 (Manahan-Vaughan, D, 1997).…”

Modulation of Neurological Deficits and Expression of Glutamate Receptors during Experimental Autoimmune Encephalomyelitis after Treatment with Selected Antagonists of Glutamate Receptors

“…While ionotropic NMDA-, AMPA-, and kainate-type glutamate receptors (iGluRs) mediate fast synaptic transmission, metabotropic glutamate receptors (mGluRs) (mGluR1 and mGluR5) modulate neuronal excitability and development, synaptic plasticity, transmitter release, and memory function via a variety of intracellular second messenger systems [11–13]. Functional interactions between ionotropic and group I metabotropic glutamate receptors have been identified.…”

Phylogeny and expression divergence of metabotropic glutamate receptor genes in the brain of zebrafish (Danio rerio)

“…Ohishi et al, 1993;Kinoshita et al, 1998;Cirone et al, 2002b). At the functional level a contribution of group I, II, and III mGluRs to the modulation of synaptic signaling in the superior colliculus of rats Salt 2000, 2001;Cirone et al, 2002a;White et al, 2003) has been reported.…”