Characterization of the metabotropic glutamate receptors (mGluRs) which modulate GABA-mediated inhibition in the ventrobasal thalamus.
The ventrobasal thalamus (VB) relays and processes somatosensory information ascending to the cerebral cortex. Several types of mGluR are known to be present in VB, and we have previously shown that Group II and Group III mGluR agonists can reduce inhibitory synaptic transmission by acting at presynaptic receptors on GABAergic terminals in this structure. We have tested the action of several antagonists against the disinhibitory action of the Group II agonist CCG-I [(2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine] and the Group III agonist L-AP4 [L-2-amino-4-phosphonobutyrate] in the VB of anaesthetized rats using extracellular single-neurone recording techniques and iontophoretic applications of mGluR antagonists and agonists. The antagonists MAP4 [alpha-methyl-L-AP4] and MPPG [(+/-)-alpha-methyl-4-phosphonophenylglycine] reduced the disinhibitory actions of L-AP4 whilst having little effect on the disinhibitory action of CCG-I. In contrast, MCCG [alpha-methyl-CCG-I] and MCPG [(+)-alpha-methyl-4-carboxyphenylglycine] antagonized CCG-I, whilst having less effect against L-AP4 responses. These results support the hypothesis that GABAergic inhibitory transmission in VB can be modulated by at least two types of mGluR, belonging to Group II and Group III. Furthermore, the novel antagonists appear to be useful tools for the future study of the physiological role of these receptors in thalamic sensory processing.
Salt
T E
TE
Department of Visual Science, University College London, U.K.
Eaton
S A
SA
Turner
J P
JP
D000200:Action Potentials / Q000502:physiology; D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D017661:Receptors, Presynaptic / Q000187:drug effects; D013787:Thalamic Nuclei / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
C089837:2-methyl-2-(2-carboxycyclopropyl)glycine; D000600:Amino Acids, Dicarboxylic; D000613:Aminobutyrates; D001565:Benzoates; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D017661:Receptors, Presynaptic; C101185:alpha-methyl-4-phosphonophenylglycine; C079694:alpha-methyl-4-carboxyphenylglycine; C035261:(alpha-carboxycyclopropyl)glycine; D005680:gamma-Aminobutyric Acid; C012729:2-amino-4-phosphonobutyric acid; D000409:Alanine; D005998:Glycine