Morphological evidence for dopamine interactions with pallidal neurons in primates.

Martin Parent,Lara Eid

doi:10.3389/fnana.2015.00111

Abstract

The external (GPe) and internal (GPi) segments of the primate globus pallidus receive dopamine (DA) axonal projections arising mainly from the substantia nigra pars compacta and this innervation is here described based on tyrosine hydroxylase (TH) immunohistochemical observations gathered in the squirrel monkey (Saimiri sciureus). At the light microscopic level, unbiased stereological quantification of TH positive (+) axon varicosities reveals a similar density of innervation in the GPe (0.19 ± 0.02 × 106 axon varicosities/mm3 of tissue) and GPi (0.17 ± 0.01 × 106), but regional variations occur in the anteroposterior and dorsoventral axes in both GPe and GPi and along the mediolateral plane in the GPe. Estimation of the neuronal population in the GPe (3.47 ± 0.15 × 103 neurons/mm3) and GPi (2.69 ± 0.18 × 103) yields a mean ratio of, respectively, 28 ± 3 and 68 ± 15 TH+ axon varicosities/pallidal neuron. At the electron microscopic level, TH+ axon varicosities in the GPe appear significantly smaller than those in the GPi and very few TH+ axon varicosities are engaged in synaptic contacts in the GPe (17 ± 3%) and the GPi (15 ± 4%) compared to their unlabeled counterparts (77 ± 6 and 50 ± 12%, respectively). Genuine synaptic contacts made by TH+ axon varicosities in the GPe and GPi are of the symmetrical and asymmetrical type. Such synaptic contacts together with the presence of numerous synaptic vesicles in all TH+ axon varicosities observed in the GPe and GPi support the functionality of the DA pallidal innervation. By virtue of its predominantly volumic mode of action, DA appears to exert a key modulatory effect upon pallidal neurons in concert with the more direct GABAergic inhibitory and glutamatergic excitatory actions of the striatum and subthalamic nucleus. We argue that the DA pallidal innervation plays a major role in the functional organization of the primate basal ganglia under both normal and pathological conditions.

Highlights

The majority of DA receptors are located presynaptically on the striatopallidal axons (Kliem et al, 2007; Hadipour-Niktarash et al, 2012). Those terminating in the external segment of the globus pallidus (GPe), which is reciprocally linked with the subthalamic nucleus, are believed to derive from medium spiny striatal neurons expressing the D2 receptor type, whereas those that arborize in the internal segment of the globus pallidus (GPi), a major output structure of the basal ganglia, are thought to emerge from medium spiny striatal neurons expressing the D1 receptor type (Yung et al, 1995; Gerfen and Bolam, 2010)
tyrosine hydroxylase (TH)+ fibers appear less numerous in the GPe than in the GPi and the proportion of the two types of labeled axons varies between pallidal segments, as well as from one region to another
The morphological, topographical, and ultrastructural data gathered in the present study has shed a new light on the anatomical substratum whereby DA exerts its influence on the primate pallidum

Summary

Introduction

The functional importance of the dopamine (DA) neurons located in the brainstem substantia nigra pars compacta (SNc) is underlined by their role in the pathophysiology of Parkinson’s disease (Penney and Young, 1983; Albin et al, 1989; Goto et al, 1989; Smith and Kieval, 2000; Rommelfanger and Wichmann, 2010; Benazzouz et al, 2014) Axons of these neurons arborize extensively in the striatum (Fallon and Moore, 1978; Lindvall and Björklund, 1979; Cossette et al, 1999; Prensa et al, 2000) where they modulate the activity of the medium spiny neurons that project to the external (GPe) and internal (GPi) segments of the globus pallidus, as well as to the substantia nigra pars reticulata (Penney and Young, 1983; Albin et al, 1989; Parent and Hazrati, 1995). On a more functional point of vue, injections of D1 or D2 receptor agonists or antagonists were shown to either increase or decrease the firing rates of pallidal neurons in rats (Qi and Chen, 2011) and monkeys (Kliem et al, 2007; Hadipour-Niktarash et al, 2012)

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Conclusion