Dopamine D₁Receptors Facilitate GABA_ASynaptic Currents in the Rat Substantia Nigra Pars Reticulata

Abstract

GABA neurons in the substantia nigra pars reticulata receive input from GABAergic fibers originating in the forebrain. The role of dopaminergic D1 receptors located on these fibers was investigated using tight-seal whole-cell recordings from visually identified pars reticulata neurons of rat substantia nigra slices. Nondopaminergic pars reticulata neurons were characterized by their electrophysiological properties. Postsynaptic currents evoked by minimal stimulation in the presence of ionotropic glutamate receptor antagonists were blocked by bicuculline, indicating that they were GABAA IPSCs. Evoked GABAA IPSCs were potentiated by D1 receptor agonists. After application of D1 receptor agonists, miniature IPSCs [recorded in the presence of tetrodotoxin (TTX) and the Ca2+ channel blocker Cd2+] increased in frequency but not in amplitude. Effects of D1 receptor stimulation were mimicked by forskolin, as expected, if a cAMP-dependent mechanism was involved. The D1 antagonist SCH23390 blocked the effects of the agonists, and perfusion with SCH23390 resulted in a reduction of evoked IPSCs. In TTX and Cd2+, which prevented dopamine release, the D1 antagonist had no effect on miniature IPSCs. Blocking of monoamine uptake by imipramine increased the amplitude of evoked IPSCs. We conclude that dopamine released from dendrites of dopaminergic neurons enhances GABA release in the pars reticulata of the substantia nigra through D1 receptors presumably located on striatonigral afferents. These D1 receptors, thereby, can reinforce D1 receptor-mediated activation of striatal projection neurons that inhibit the inhibitory output neurons of the basal ganglia in substantia nigra.

Dopaminergic Modulation of Axon Collaterals Interconnecting Spiny Neurons of the Rat Striatum

“…With this method, a presynaptic D 2 -mediated modulation similar to that shown on the striatopallidal pathway (Cooper and Stanford, 2001;Mengual and Pickel, 2002) or in the cholinergic or fastspiking (FS) interneurons (Pisani et al, 2000;Momiyama and Koga, 2001;Centonze et al, 2003) was shown. Similarly, a presynaptic modulation by D 1 receptor agonists as that reported in the striatonigral pathway (Floran et al, 1990(Floran et al, , 1997Cameron and Williams, 1993;Radnikow and Misgeld, 1998) was also shown, despite postsynaptic dopaminergic actions (Pacheco-Cano et al, 1996) on the subthreshold inward rectification Nisenbaum and Wilson, 1995;Mermelstein et al, 1998;Farries and Perkel, 2000) that shunts inhibitory inputs (Fitzpatrick et al, 2001).…”

“…If that were true, a consistent dopaminergic modulation should be seen, which was the case, resulting in the initial description of this modulation. In addition, neostriatal projection neurons express D 1 or D 2 receptors (Surmeier et al, 1993;Hernandez-Lopez et al, 1997, 2000Aizman et al, 2000), and consistent presynaptic actions as the result of the activation of these receptors have been reported at the target nuclei (Floran et al, 1990(Floran et al, , 1997Cameron and Williams, 1993;Radnikow and Misgeld, 1998;Cooper and Stanford, 2001). Moreover, D 1 postsynaptic actions are facilitatory (Hernandez-Lopez et al, 1997), whereas D 2 postsynaptic actions depress firing (Hernandez-Lopez et al, 2000) in spiny neurons.…”

“…On the other hand, although PPR did not change consistently during D 1 receptor agonists, a significant and consistent decrease in IPSCs amplitude was seen, suggesting a mixture of postsynaptic (Flores-Hernández et al, 2000) and presynaptic (Centonze et al, 2003;Gao et al, 2003) D 1 effects. This latter effect is the opposite of that found on IPSCs from axon collaterals and striatonigral terminals (Radnikow and Misgeld, 1998), demonstrating that the same modulator may have opposite actions on different GABAergic connections and neurons.…”

“…Synaptic terminals from spiny neurons are presynaptically modulated by dopamine at their target nuclei (e.g., pallidum and substantia nigra reticulata) (Floran et al, 1990(Floran et al, , 1997Radnikow and Misgeld, 1998;Cooper and Stanford, 2001). Consequently, our hypothesis was that the same type of regulation should be present within the neostriatum.…”

“…The globus pallidus (GP) was first lesioned with ibotenic acid to destroy intrinsic pallidal cells. Related questions were whether modulation produced by D 1 receptor agonists is different from, or even opposed to, that produced by D 2 receptor agonists (Floran et al, 1990(Floran et al, , 1997Radnikow and Misgeld, 1998;Cooper and Stanford, 2001) and whether spiny neurons from the direct and the indirect pathways (Gerfen and Young, 1988;Albin et al, 1989) are synaptically interconnected (Aronin et al, 1986;Bolam and Izzo, 1988;Yung et al, 1996).…”