Modulation of dopamine neuronal activity by glutamate receptor subtypes

In vitro and in vivo electrophysiological studies have been used to assess the effects of glutamate, as well as specific agonists and antagonists for ionotropic, N-methyl-D-aspartate (NMDA), (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate, and metabotropic subtypes of the glutamate receptor, on the neuronal firing activity of midbrain, substantia nigra zona compacta (A9) and ventral tegmental area (A10), dopamine neurons. In in vitro experiments, agonists for all glutamate receptor subtypes depolarize the membrane and increase firing rate. In in vivo experiments, iontophoretic application of these agonists increases the firing rate and induces burst-firing. Studies with subtype selective antagonists suggest that a tonic glutamate tone, acting via NMDA receptors, may modulate the firing activity of some dopamine neurons. Glutamatergic afferents from the subthalamus, pedunculopontine nucleus and frontal cortex can modulate the firing activity of dopamine neurons. The role(s) of the different glutamate receptor subtypes and pathways in mediating the physiological and pathological effects on dopamine systems is an area for further investigation.