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

Eur J Neurosci. 2020 Dec;52(11):4563-4585. doi: 10.1111/ejn.15020. Epub 2020 Nov 8.

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.

Keywords: GABA release; Globus pallidus; dopamine; turning behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corpus Striatum / metabolism
  • Dopamine
  • Globus Pallidus* / metabolism
  • Mice
  • Rats
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D4*

Substances

  • Receptors, Dopamine D1
  • Receptors, Dopamine D4
  • Dopamine