Activation of Group II and Group III metabotropic glutamate receptors by endogenous ligand(s) and the modulation of synaptic transmission in the superficial superior colliculus

Abstract

Previous work from this laboratory indicates that Group II/III metabotropic glutamate (mGlu) receptors modulate responses of SC neurones to visual stimuli in vivo. It is thought that tonic levels of glutamate may be sufficient to activate some mGlu receptors. We wished to investigate if these receptors are activated under ambient conditions in SC. Field excitatory postsynaptic potentials (fEPSPs) evoked by optic tract stimulation were recorded from 300 μm slices of the adult pigmented rat superior colliculus at 34 °C. The Group II receptor selective agonist LY354740 (100–300 nM) had no significant effect on the peak amplitude of the fEPSP, although it did enhance the late phase of the fEPSP. In order to test for activation of Group II receptors by endogenous ligand, the selective antagonists LY341495 (50 nM) or EGLU (200 μM) were applied: these either enhanced or reduced the fEPSP amplitude. In similar experiments carried out at 22 °C, no effect was seen. The fEPSP enhancements, but not the fEPSP reductions, could be occluded by GABA antagonists. Application of higher concentrations of LY341495 (300, 600 nM—known to also affect Group III receptors, particularly mGlu8), or co-application of 50 nM LY341495 and the Group III-selective antagonist CPPG (100 μM) produced enhancements of responses, or counteracted response reductions over those seen with 50 nM LY341495 alone. The predominant Group II receptor in SC is mGlu3. It is known that this can be located presynaptically on GABAergic and glutamatergic terminals, postsynaptically, and on glia. Our results indicate that such receptors are tonically activated by endogenous transmitter, have distinct effects, and influence retino-collicular transmission. Furthermore, there is a segregation of effects where receptors exert some of their effects via modulation of GABAergic circuitry.