Control of the Subthalamic Innervation of Substantia Nigra Pars Reticulata by D₁ and D₂ Dopamine Receptors

Abstract

. Control of the subthalamic innervation of substantia nigra pars reticulata by D 1 and D 2 dopamine receptors. J Neurophysiol 95: 1800 -1811, 2006. First published November 23, 2005 doi:10.1152/jn.01074.2005. The effects of activating dopaminergic D 1 and D 2 class receptors of the subthalamic projections that innervate the pars reticulata of the subtantia nigra (SNr) were explored in slices of the rat brain using the whole cell patch-clamp technique. Excitatory postsynaptic currents (EPSCs) that could be blocked by 6-cyano-7-nitroquinoxalene-2,3-dione and D-(Ϫ)-2-amino-5-phosphonopentanoic acid were evoked onto reticulata GABAergic projection neurons by local field stimulation inside the subthalamic nucleus in the presence of bicuculline. Bath application of (RS)-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF-38393), a dopaminergic D 1 -class receptor agonist, increased evoked EPSCs by ϳ30% whereas the D 2 -class receptor agonist, trans-(Ϫ)- 4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo(3,4-g)quinoline (quinpirole), reduced EPSCs by ϳ25%. These apparently opposing actions were blocked by the specific D 1 -and D 2 -class receptor antagonists: R-(ϩ)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetra-hydro-1H-3-benzazepine hydrochloride (SCH 23390) and S-(Ϫ) -5-anino-sulfonyl-N-[(1-ethyl-2-pyrrolidinyl)-methyl]-2-methoxybenzamide (sulpiride), respectively. Both effects were accompanied by changes in the paired-pulse ratio, indicative of a presynaptic site of action. The presynaptic location of dopamine receptors at the subthalamonigral projections was confirmed by mean-variance analysis. The effects of both SKF-38393 and quinpirole could be observed on terminals contacting the same postsynaptic neuron. Sulpiride and SCH 23390 enhanced and reduced the evoked EPSC, respectively, suggesting a constitutive receptor activation probably arising from endogenous dopamine. These data suggest that dopamine presynaptically modulates the subthalamic projection that targets GABAergic neurons of the SNr. Implications of this modulation for basal ganglia function are discussed.

A Calcium-Activated Nonselective Cation Conductance Underlies the Plateau Potential in Rat Substantia Nigra GABAergic Neurons

“…Nigral GABAergic neurons receive a glutamatergic input from the subthalamic nucleus Van Der Kooy and Hattori, 1980;Robledo and Feger, 1990;Bevan et al, 1994;Iribe et al, 1999;Ibanez-Sandoval et al, 2006) and can respond to stimulation of the subthalamic nucleus with plateau potentials (Nakanishi et al, 1987b). We have shown here that one mechanism that can elicit the plateau potential is NMDA receptor activation.…”

Bidirectional plasticity in striatonigral synapses: A switch to balance direct and indirect basal ganglia pathways

“…The first condition includes both 10 mM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an AMPA/KA-receptor antagonist, plus 50 mM (2R)-amino-5-phosphonovaleric acid (APV), a NMDA-receptor antagonist ( Fig. 1A; Ibañez-Sandoval et al 2006;Rueda-Orozco et al 2009) . In this situation, IPSCs undergo a brief period of post-tetanic potentiation and thereafter maintain increased amplitude, as compared with the controls, for .20 min after HFS.…”

“…The substantia nigra pars reticulata (SNr) and the internal segment of the globus pallidus (GPi) are the output nuclei of the BG receiving converging entries from both direct and indirect BG pathways (Alexander et al 1986;Alexander and Crutcher 1990;Radnikow and Misgeld 1998;Smith et al 1998;Ibañez-Sandoval et al 2006;Deniau et al 2007). Probably a choice of whether an action is executed or not occurs in these nuclei (Sarvestani et al 2011), since according to the "two pathways model" (Albin et al 1989), direct pathway activation facilitates, whereas indirect pathway activation represses movements (Wichmann and DeLong 2003;Graybiel 2004;Grillner et al 2005;DeLong and Wichmann 2007;Ibañez-Sandoval et al 2007;Bateup et al 2010;Kravitz et al 2010).…”

“…It is known that dopaminergic fibers and neurons innervate SNr (Misgeld 2004;Zhou et al 2009;Rommelfanger and Wichmann 2010) and that they modulate its afferents: striatonigral (direct pathway) (Cameron and Williams 1993;Radnikow and Misgeld 1998;Aceves et al 2011;Chuhma et al 2011) and subthalamonigral (indirect pathway) (Ibañez-Sandoval et al 2006) via presynaptic receptors (Yanovsky et al 2003;Misgeld et al 2007). Accordingly, here we study the dopaminergic modulation of striatonigral synapses and propose its possible role in the selection mechanism.…”

“…Consequently, the direct pathway synapses may exhibit an enhancement or decrease in its output, depending on the coincidence, or not, of active postsynaptic NMDA receptors. Because the indirect pathway (subthalamonigral synapses) is a main source for activating NMDA receptors in SNr neurons (Nakanishi et al 1987;Robledo and Feger 1990;Ibañez-Sandoval et al 2006;DeLong and Wichmann 2007), it is concluded that a coincidence of inputs from both pathways may lead to LTD, whereas a mismatch in their arrival leads to the opposite result.…”