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

多巴胺 D4 受体调节苍白球-苍白球终末细胞中的抑制性传递并调节运动行为

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作者:Israel Conde Rojas, Jackeline Acosta-García, Rene Nahum Caballero-Florán, Rafael Jijón-Lorenzo, Sergio Recillas-Morales, José Arturo Avalos-Fuentes, Francisco Paz-Bermúdez, Gerardo Leyva-Gómez, Hernán Cortés, Benjamín Florán

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: 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.

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