DISTINCT PRESYNAPTIC METABOTROPIC RECEPTORS FOR L-AP4 AND CCG1 ON GABAERGIC TERMINALS - PHARMACOLOGICAL EVIDENCE USING NOVEL ALPHA-METHYL DERIVATIVE MGLUR ANTAGONISTS, MAP4 AND MCCG, IN THE RAT THALAMUS IN-VIVO

A variety of metabotropic excitatory amino acid receptors are present in the thalamus. We have investigated the possibility that some of these receptors may have presynaptic effects on GABAergic inhibitory transmission in the thalamus. Inhibitory responses in ventrobasal thalamic neurons of urethane-anaesthetized rats were evoked by either air-jet stimuli to the vibrissae or by electrical stimulation of the somatosensory cortex. Both intracellular and extracellular recording methods were used to reveal inhibitory responses, either as inhibitory postsynaptic potentials or inhibition of excitatory responses in a condition-test paradigm. The metabotropic glutamate receptor agonists (S)-2-amino-4-phosphonobutyrate (L-AP4) and (2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine (CCGl), applied in the vicinity of the recording site by iontophoresis, were found to reduce the amplitudes of inhibitory postsynaptic potentials (to 76% and 63% of control amplitudes, respectively) and inhibitions revealed by the condition-test paradigm (to 33% and 28% of control inhibitions, respectively). As the inhibitory responses arise from the neurons of the nucleus reticularis thalami, some distance away from the site of recording and iontophoretic drug application, it is likely that the reduction of inhibition seen with L-AP4 and CCGl is due to an action of these agonists on the terminals or axons of these inhibitory neurons. The novel antagonists of L-AP4 and CCGl, alpha-methyl-L-AP4, and alpha-methyl-CCGl, were found to block the disinhibitory actions of the agonists in a differential manner when applied iontophoretically. This suggests that there may be at least two types of receptor mediating the disinhibitory effects. These receptors might be one or more of the metabotropic glutamate receptor 2,3 or metabotropic glutamate receptor 4,7 variety, and could have a function in the modulation of the temporal and spatial response patterns of thalamic neurons to sensory inputs.