Differential calcium channel-mediated dopaminergic modulation in the subthalamonigral synapse

Dopamine (DA) modulates basal ganglia (BG) activity for initiation and execution of goal-directed movements and habits. While most studies are aimed to striatal function, the cellular and molecular mechanisms underlying dopaminergic regulation in other nuclei of the BG are not well understood. Therefore, we set to analyze the dopaminergic modulation occurring in subthalamo-nigral synapse, in both pars compacta (SNc) and pars reticulata (SNr) neurons, because these synapses are important for the integration of information previously processed in striatum and globus pallidus. In this study, electrophysiological and pharmacological evidence of dopaminergic modulation on glutamate release through calcium channels is presented. Using paired pulse ratio (PPR) measurements and selective blockers of these ionic channels, together with agonists and antagonists of DA D₂ -like receptors, we found that blockade of the Ca_V 3 family occludes the presynaptic inhibition produced by the activation of DA receptors pharmacologically profiled as D₃ -type in the STh-SNc synapses. On the contrast, the blockade of Ca_V 2 channels, but not Ca_V 3, occlude with the effect of the D₃ agonist, PD 128907, in the STh-SNr synapse. The functional role of this differential distribution of calcium channels that modulate the release of glutamate in the SN implies a fine adjustment of firing for both classes of neurons. Dopaminergic neurons of the SNc establish a DA tone within the SN based on the excitatory/inhibitory inputs; such tone may contribute to processing information from subthalamic nucleus and could also be involved in pathological DA depletion that drives hyperexcitation of SNr neurons.