Dopaminergic control of the globus pallidus through activation of D2 receptors and its impact on the electrical activity of subthalamic nucleus and substantia nigra reticulata neurons.

David I Finkelstein,Omar Mamad,Wail Benjelloun,Claire Delaville,Abdelhamid Benazzouz

doi:10.1371/journal.pone.0119152

Abstract

The globus pallidus (GP) receives dopaminergic afferents from the pars compacta of substantia nigra and several studies suggested that dopamine exerts its action in the GP through presynaptic D2 receptors (D2Rs). However, the impact of dopamine in GP on the pallido-subthalamic and pallido-nigral neurotransmission is not known. Here, we investigated the role of dopamine, through activation of D2Rs, in the modulation of GP neuronal activity and its impact on the electrical activity of subthalamic nucleus (STN) and substantia nigra reticulata (SNr) neurons. Extracellular recordings combined with local intracerebral microinjection of drugs were done in male Sprague-Dawley rats under urethane anesthesia. We showed that dopamine, when injected locally, increased the firing rate of the majority of neurons in the GP. This increase of the firing rate was mimicked by quinpirole, a D2R agonist, and prevented by sulpiride, a D2R antagonist. In parallel, the injection of dopamine, as well as quinpirole, in the GP reduced the firing rate of majority of STN and SNr neurons. However, neither dopamine nor quinpirole changed the tonic discharge pattern of GP, STN and SNr neurons. Our results are the first to demonstrate that dopamine through activation of D2Rs located in the GP plays an important role in the modulation of GP-STN and GP-SNr neurotransmission and consequently controls STN and SNr neuronal firing. Moreover, we provide evidence that dopamine modulate the firing rate but not the pattern of GP neurons, which in turn control the firing rate, but not the pattern of STN and SNr neurons.

Highlights

The globus pallidus (GP, the rodent homologue of the primate globus pallidus externus, GPe) is a basal ganglia structure playing a key role in the control of movement
Given the predominance of D2 receptors (D2Rs) in GP and that most actions of dopamine in the GP are mediated by D2Rs [5], we investigated the role of dopamine, through activation of D2Rs, in the control of GP neuronal activity using in vivo extracellular recordings in the rat
The firing rate increase, which represents the major effect of dopamine on GP neurons, may be explained by the action of this neurotransmitter on D2Rs located pre-synaptically on GABA striato-pallidal fibers [6]

Summary

Introduction

The globus pallidus (GP, the rodent homologue of the primate globus pallidus externus, GPe) is a basal ganglia structure playing a key role in the control of movement. It is considered as an inhibitory GABAergic relay in the indirect pathway, linking the striatum to the pars reticulata of substantia nigra (SNr), directly or indirectly via the subthalamic nucleus (STN) [1]. While the striatum is by far the main target of SNc dopamine neurons, dopamine mediates its regulatory function at the level of GP [5,6] Both dopamine D1 (D1R) and D2 (D2R) receptor families are expressed in the GP with a predominance of D2Rs [7]. From a functional point of view, a major role of dopamine in the modulation of GP neuronal activity has been suggested by studies demonstrating that intrapallidal dopamine receptor blockade [9] or dopamine depletion [10] produced motor deficits in rodents that can be associated with a reduction of the firing rate of GP neurons [11,12]

Methods

Results

Conclusion