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

2020; Wiley; Volume: 52; Issue: 11 Linguagem: Inglês

10.1111/ejn.15020

1460-9568

Israel Conde Rojas, Jackeline Acosta‐García, René N. Caballero-Florán, Rafael Jijón‐Lorenzo, Sergio Recillas‐Morales, José Arturo Ávalos‐Fuentes, Francisco Paz‐Bermúdez, Gerardo Leyva‐Gómez, Hernán Cortés, Benjamí­n Florán,

Neuroscience and Neuropharmacology Research

Abstract 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: D 2 R subtype is expressed by encephalin‐positive MSNs, while pallidal neurons express the D 4 R subtype. The D 2 R modulates the firing rate of striatal neurons and GABA release at their projection areas, while the D 4 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 D 4 R in pallidal synaptosomes, control of [ 3 H] GABA release in pallidal slices of rat, electrophysiological evidence of the presence of D 4 R on pallidal recurrent collaterals in mouse slices, and turning behavior induced by D 4 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 D 4 R, while the D 2 R subtype, as known, modulates striato‐pallidal projections. Also, as in projection areas, D 4 R contributes to control the motor activity differently than D 2 R. This study could help to understand the organization of intra‐pallidal circuitry.