Dopaminergic Presynaptic Modulation of Nigral Afferents: Its Role in the Generation of Recurrent Bursting in Substantia Nigra Pars Reticulata Neurons

Elvira Galarraga,José Bargas,José De Jesús Aceves,Osvaldo Ibañez-Sandoval,Pavel E Rueda-Orozco,Ricardo Hernández,Víctor Plata

doi:10.3389/fnsys.2011.00006

Elvira Galarraga, José Bargas + Show 5 more

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https://doi.org/10.3389/fnsys.2011.00006

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Abstract

Previous work has shown the functions associated with activation of dopamine presynaptic receptors in some substantia nigra pars reticulata (SNr) afferents: (i) striatonigral terminals (direct pathway) posses presynaptic dopamine D1-class receptors whose action is to enhance inhibitory postsynaptic currents (IPSCs) and GABA transmission. (ii) Subthalamonigral terminals posses D1- and D2-class receptors where D1-class receptor activation enhances and D2-class receptor activation decreases excitatory postsynaptic currents. Here we report that pallidonigral afferents posses D2-class receptors (D3 and D4 types) that decrease inhibitory synaptic transmission via presynaptic modulation. No action of D1-class agonists was found on pallidonigral synapses. In contrast, administration of D1-receptor antagonists greatly decreased striatonigral IPSCs in the same preparation, suggesting that tonic dopamine levels help in maintaining the function of the striatonigral (direct) pathway. When both D3 and D4 type receptors were blocked, pallidonigral IPSCs increased in amplitude while striatonigral connections had no significant change, suggesting that tonic dopamine levels are repressing a powerful inhibition conveyed by pallidonigral synapses (a branch of the indirect pathway). We then blocked both D1- and D2-class receptors to acutely decrease direct pathway (striatonigral) and enhance indirect pathways (subthalamonigral and pallidonigral) synaptic force. The result was that most SNr projection neurons entered a recurrent bursting firing mode similar to that observed during Parkinsonism in both patients and animal models. These results raise the question as to whether the lack of dopamine in basal ganglia output nuclei is enough to generate some pathological signs of Parkinsonism.

Highlights

The internal globus pallidus (GPi) and substantia nigra pars reticulata (SNr) are the basal ganglia (BG) output nuclei
In the SNr, inhibitory postsynaptic currents (IPSCs) are in part provided by striatonigral direct pathway terminals (Grofová and Rinvik, 1970; Chevalier et al, 1985; Smith and Bolam, 1991; Deniau et al, 1996; Matuszewich and Yamamoto, 1999), which possess functional presynaptic dopamine D1-receptors whose activation increases direct pathway inhibition (Porceddu et al, 1986; Altar and Hauser, 1987; Floran et al, 1990; Radnikow and Misgeld, 1998; Chuhma et al, 2011)
Activation of D1 enhances while activation of D2 depresses subthalamonigral excitatory postsynaptic currents (EPSCs)

Summary

Introduction

The internal globus pallidus (GPi) and substantia nigra pars reticulata (SNr) are the basal ganglia (BG) output nuclei. Besides projecting to the thalamus to form the cortico-BG loops (Chevalier et al, 1985; Albin et al, 1989; Smith and Bolam, 1989; Alexander and Crutcher, 1990; DeLong, 1990; Smith et al, 1998; Haber, 2003), output nuclei project to pons and brain stem to control descending pathways and central patterns generators (CPGs) that regulate muscular tone and automatic or rhythmic motor responses (Takakusaki et al, 2003, 2004; Grillner et al, 2008). Simultaneous blockade of both receptors induced larger evoked EPSCs, suggesting that

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