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1 Physiology, CINVESTAV, Mexico City, DF, Mexico
2 Biofisica, Instituto de Fisiologia celular UNAM, Mexico City, DF, Mexico
3 Biofisica, Instituto de Fisiologia Celular UNAM, Mexico, DF, Mexico; Biofisica, IFC-UNAM, Mexico, DF, Mexico
4 Neurociencias, FES-Iztacala UNAM, Los Reyes Iztacala, Mexico, Mexico
5 Biofisica, Instituto de Fisologia Celular UNAM, Mexico, DF, Mexico; Biofisica, IFC-UNAM, Mexico, DF, Mexico
6 Biofisica, Instituto de Fisiologia Celular UNAM, Mexico City, DF, Mexico
* To whom correspondence should be addressed. E-mail: jbargas{at}ifc.unam.mx.
The effects of activating dopaminergic D2/3 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, 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 D2/3 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 EPSC reduction that was sulpiride-resistant 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 sEPSCs amplitude; indicative of a postsynaptic site of action. These results show that dopamine modulates subthalamopallidal excitation via presynaptic D2/3 and postsynaptic D4 receptors. The importance of this modulation is discussed.
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