Dopamine D4 receptor modulates inhibitory transmission in pallido-pallidal terminals and regulates motor behavior

Two major groups of terminals release GABA within the Globus pallidus; one group is constituted by projections from striatal neurons, while endings of the intranuclear collaterals form the other one. Each neurons' population expresses different subtypes of dopamine D2-like receptors: D2R subtype is expressed by encephalin-positive MSNs, while pallidal neurons express the D4R subtype. The D2R modulates the firing rate of striatal neurons and GABA release at their projection areas, while the D4R regulates Globus pallidus neurons excitability and GABA release at their projection areas. However, it is unknown if these receptors control GABA release at pallido-pallidal collaterals and regulate motor behavior. Here, we present neurochemical evidence of protein content and binding of D4R in pallidal synaptosomes, control of [H-3] GABA release in pallidal slices of rat, electrophysiological evidence of the presence of D4R on pallidal recurrent collaterals in mouse slices, and turning behavior induced by D4R antagonist microinjected in amphetamine challenged rats. As in projection areas of pallidal neurons, GABAergic transmission in pallido-pallidal recurrent synapses is under modulation of D4R, while the D2R subtype, as known, modulates striato-pallidal projections. Also, as in projection areas, D4R contributes to control the motor activity differently than D2R. This study could help to understand the organization of intra-pallidal circuitry.