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Presynaptic Actions of D2-Like Receptors in the Rat Cortico-Striato-Globus Pallidus Disynaptic Connection In Vitro

Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis, Tennessee

Submitted 24 July 2008; accepted in final form 2 December 2008

The cerebral cortex, the neostriatum (Str), and the external segment of the globus pallidus (GPe) form a cortico-Str-GPe disynaptic connection, which is one of the major connections in the basal ganglia circuitries and a target of dopamine modulation. The aim of this study was to examine the actions of D2-like dopamine receptors (D2LRs) in this connection using rat brain slice preparations. Electrical stimulation of the frontal cortex evoked disynaptic inhibitory postsynaptic currents (IPSCs) in cesium-filled GPe neurons voltage-clamped at 0 mV. The IPSCs evoked by threshold stimulation were small, <10 pA. Bath or local applications of the D2LR agonist quinpirole to Str decreased the amplitude of the cortical stimulation-induced IPSCs. Electrical stimulation of Str evoked monosynaptic IPSCs in GPe neurons. Local application of quinpirole to GPe decreased the Str stimulation-induced IPSCs. Bath application of quinpirole decreased the frequency of large miniature IPSCs (mIPSCs) that were considered to be evoked by local collateral axons of GPe neurons. These results suggested that activation of D2LRs decrease the gain of the cortico-Str-GPe disynaptic connection, with the decrease attributed to activation of D2LRs in Str and GPe, and that both Str-GPe and GPe-GPe GABAergic inhibitions are under the control of presynaptic D2LRs.