Control of the Subthalamic Innervation of the Rat Globus Pallidus by D2/3 and D4 Dopamine Receptors

Abstract

The effects of activating dopaminergic D_2/3 and D₄ receptors during activation of the subthalamic projection to the globus pallidus (GP) were explored in rat brain slices using the whole cell patch-clamp technique. Byocitin labeling and both orthodromic and antidromic activation demonstrated the integrity of some subthalamopallidal connections in in vitro parasagittal brain slices. Excitatory postsynaptic currents (EPSCs) that could be blocked by CNQX and AP5 were evoked onto pallidal neurons by local field stimulation of the subthalamopallidal pathway in the presence of bicuculline. Bath application of dopamine and quinpirole, a dopaminergic D₂-class receptor agonist, reduced evoked EPSCs by about 35%. This effect was only partially blocked by sulpiride, a D_2/3 receptor antagonist. The sulpiride-sensitive reduction of the subthalamopallidal EPSC was associated with an increase in the paired-pulse ratio (PPR) and a reduction in the frequency but not the mean amplitude of spontaneous EPSCs (sEPSCs), indicative of a presynaptic site of action, which was confirmed by variance–mean analysis. The sulpiride-resistant EPSC reduction was mimicked by PD 168,077 and blocked by L-745,870, selective D₄ receptor agonist and antagonist, respectively, suggesting the involvement of D₄ receptors. The reduction of EPSCs produced by PD 168,077 was not accompanied by changes in PPR or the frequency of sEPSCs; however, it was accompanied by a reduction in mean sEPSC amplitude, indicative of a postsynaptic site of action. These results show that dopamine modulates subthalamopallidal excitation by presynaptic D_2/3 and postsynaptic D₄ receptors. The importance of this modulation is discussed.