Excitation of rat subthalamic nucleus neurones in vitro by activation of a group I metabotropic glutamate receptor

Abstract

The subthalamic nucleus (SThN) provides a glutamate mediated excitatory drive to several other component nuclei of the basal ganglia, thereby significantly influencing locomotion and control of voluntary movement. We have characterised functionally the metabotropic glutamate (mGlu) receptors in the SThN using extracellular single unit recording from rat midbrain slices. SThN neurones fired action potentials spontaneously at a rate of 10 Hz which was increased by the group I/II mGlu receptor agonist (1S,3R)-1- amino-cyclopentane-1,3-dicarboxylate (1S,3R-ACPD; 1-30 μM) and the group I selective agonist (S,R)-dihydroxyphenylglycine (DHPG; 1-30 μM). However, both the group II selective agonist (1S, 1'R,2'R,3'R)-2-(2,3- dicarboxycyclopropyl)glycine (DCG-IV; 1 μM) and the group III selective agonist (S)-2-amino-4-phosphonobutanoic acid (L-AP4; 10 μM) were without effect, indicating that the excitation was mediated by a group I mGlu receptor. The excitation caused by DHPG (3 μM) was reversed by co- application of the mGlu receptor antagonist (+)-α-methyl-4- carboxyphenylglycine (MCPG; 500 μM). Thus a group I mGlu receptor mediates excitation of SThN neurones, and suggests a use for group I mGlu receptor ligands for treatment of both hypo- and hyperkinetic disorders of basal ganglia origin, such as Parkinson's disease and Huntington's disease.