Neuroanatomical Study of the A11 Diencephalospinal Pathway in the Non-Human Primate

Quentin Barraud,Paula Ravenscroft,Gregory Porras,Imad Ghorayeb,Imad Ghorayeb,Ibrahim Obeid,Erwan Bezard,Incarnation Aubert,Hugues Contamin,François Tison,François Tison,Steve Mcguire,Gregory Barrière,Shawn Hochman

doi:10.1371/journal.pone.0013306

Abstract

BackgroundThe A11 diencephalospinal pathway is crucial for sensorimotor integration and pain control at the spinal cord level. When disrupted, it is thought to be involved in numerous painful conditions such as restless legs syndrome and migraine. Its anatomical organization, however, remains largely unknown in the non-human primate (NHP). We therefore characterized the anatomy of this pathway in the NHP.Methods and FindingsIn situ hybridization of spinal dopamine receptors showed that D1 receptor mRNA is absent while D2 and D5 receptor mRNAs are mainly expressed in the dorsal horn and D3 receptor mRNA in both the dorsal and ventral horns. Unilateral injections of the retrograde tracer Fluoro-Gold (FG) into the cervical spinal enlargement labeled A11 hypothalamic neurons quasi-exclusively among dopamine areas. Detailed immunohistochemical analysis suggested that these FG-labeled A11 neurons are tyrosine hydroxylase-positive but dopa-decarboxylase and dopamine transporter-negative, suggestive of a L-DOPAergic nucleus. Stereological cell count of A11 neurons revealed that this group is composed by 4002±501 neurons per side. A 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) intoxication with subsequent development of a parkinsonian syndrome produced a 50% neuronal cell loss in the A11 group.ConclusionThe diencephalic A11 area could be the major source of L-DOPA in the NHP spinal cord, where it may play a role in the modulation of sensorimotor integration through D2 and D3 receptors either directly or indirectly via dopamine formation in spinal dopa-decarboxylase-positives cells.

Highlights

A number of pathological conditions are related to dysregulation of dopaminergic transmission such as schizophrenia and the mesocortical system, addiction and the mesolimbic system, and Parkinson’s disease (PD) and the nigrostriatal system [1,2,3]
The diencephalic A11 area could be the major source of L-DOPA in the non-human primate (NHP) spinal cord, where it may play a role in the modulation of sensorimotor integration through D2 and D3 receptors either directly or indirectly via dopamine formation in spinal dopa-decarboxylase-positives cells
D1 and D2 receptor subtypes were mainly expressed within the striatum and cortex, D3 mainly expressed within the ventral striatum and the Islands of Calleja and D5 mainly expressed within the cortex (Fig. 1) [38]

Summary

Introduction

A number of pathological conditions are related to dysregulation of dopaminergic transmission such as schizophrenia and the mesocortical system, addiction and the mesolimbic system, and Parkinson’s disease (PD) and the nigrostriatal system [1,2,3]. Contrasting with the forebrain, the dopaminergic innervation of the spinal cord from A11 remains largely under-investigated [4,5,6] its functional implications in the spinal cord autonomic and sensory-motor processes are of particular relevance for pain control [7], cataplexy [8], locomotor network modulation [9] and painful human conditions such as restless legs syndrome (RLS) [10] and migraine [11]). Spinal release of DA has been shown to activate spinal motor networks involved in locomotion [9,18,19,20] This experimental evidence underscores the role of dopaminergic spinal innervation in the modulation of the sensory and motor processes. We characterized the anatomy of this pathway in the NHP

Methods

Results

Conclusion