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: D₂ R subtype is expressed by encephalin-positive MSNs, while pallidal neurons express the D₄ R subtype. The D₂ R modulates the firing rate of striatal neurons and GABA release at their projection areas, while the D₄ R 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 D₄ R in pallidal synaptosomes, control of [³ H] GABA release in pallidal slices of rat, electrophysiological evidence of the presence of D₄ R on pallidal recurrent collaterals in mouse slices, and turning behavior induced by D₄ R antagonist microinjected in amphetamine challenged rats. As in projection areas of pallidal neurons, GABAergic transmission in pallido-pallidal recurrent synapses is under modulation of D₄ R, while the D₂ R subtype, as known, modulates striato-pallidal projections. Also, as in projection areas, D₄ R contributes to control the motor activity differently than D₂ R. This study could help to understand the organization of intra-pallidal circuitry.