Elsevier

Neuroscience

Volume 282, 12 December 2014, Pages 243-247
Neuroscience

Review
The ventral tegmentum and dopamine: A new wave of diversity

https://doi.org/10.1016/j.neuroscience.2014.10.017Get rights and content

Highlights

  • There is a cellular and functional diversity of ventral tegmental cells.

  • Technical advances favored the study of the ventral tegmental heterogeneity.

  • Differentiating model-specific from generalized data requires comparative studies and translational effort.

Abstract

Projection systems arising from the ventral tegmental area (VTA) and the substantia nigra (SN) have a critical role in a broad range of functions, as well as in the etiology, symptoms and treatment of neurological and psychiatric diseases. Mostly studied for its dopamine neurons, the ventral tegmentum is in fact heterogeneous at cellular and functional levels. This special issue of Neuroscience gathered some experts in the field to review the connectivity of the ventral mesencephalic dopaminergic complex, its cellular heterogeneity with attention given to glutamate neurons, the D2 autoreceptor and the cholinergic controls of dopamine activity, the influence of neurotrophins, the controls of bursting activity and the heterogeneity of neuronal activity across traits and states, the pedunculopontine tegmental and the sensory controls of dopamine activity, the sex-dependent diversity, the links between circadian and dopamine systems, the functional antero-posterior heterogeneity of the VTA and the role of its GABA tail (tVTA/rostromedial tegmental nucleus (RMTg)), the functional heterogeneity of the VTA outputs, the place of dopamine in cortico-basal ganglia circuitry, the different roles of the D1 and D2 striatal pathways and the role of dopamine in associative learning and memory. Recent progress also highlights the need for molecular markers of functional subpopulations within the ventral tegmentum, for deeper developmental knowledge of this region, and for a single cell level of connectomic. It also raises the question of inter-individual, sex, strain and species heterogeneity, and conversely the question of data generalization in a context of human pathology models, which warrant comparative studies and translational effort.

Introduction

Dopamine systems are the most studied brain systems, “dopamine” retrieving close to 140,000 articles under PubMed, almost 25,000 of them published in the past 5 years. Since the description of dopamine systems in the 1960s and 1970s, accumulating evidence points to their critical role in a broad range of functions, including motor functions, motivated behavior, reward, associative learning and mood. The dopamine systems mainly arise from midbrain ventral areas harboring dopamine neuron cell bodies that project to a wide array of brain regions where they exert a modulatory influence. As a consequence of these physiological roles, dopamine systems are also implicated in the etiology, symptoms and treatment of neurological and psychiatric diseases, such as Parkinson’s disease, schizophrenia, mood disorders, attention deficit hyperactivity disorder (ADHD) and drug abuse. Understanding these systems is thus critical to help understanding the physiology of adaptation as well as the brain mechanisms underlying the pathogenesis of various neurological and mental disorders.

In the past decades, major progress has been made, which is now fostering new and exciting research avenues. The functional heterogeneity of ventral tegmental neurons, including dopamine neurons, is recognized. Considering the huge amount of published data, it is important to provide critical analyses and reviews about what has been accomplished. This special issue of Neuroscience gathered some experts in the field to review advances on specific topics, highlighting the neuronal heterogeneity of midbrain areas harboring dopamine cells, the diversity of controls exerted on dopamine systems and the respective functions of the various output pathways, pointing out some key unanswered questions.

This special issue more particularly addresses the connectivity of the ventral mesencephalic dopaminergic complex (Yetnikoff et al., 2014), and its cellular heterogeneity with attention given to glutamate neurons within the midbrain dopamine regions (Morales and Root, 2014). It also summarizes present knowledge on the D2 autoreceptor (Ford, 2014) and the cholinergic (Faure et al., 2014) controls of dopamine activity, on the influence of neurotrophins on dopamine systems (Nikulina et al., 2014, Walsh and Han, 2014), and more largely on the controls of bursting activity (Paladini and Roeper, 2014) and on the heterogeneity of dopamine neuron activity across traits and states (Marinelli and McCutcheon, 2014). The pedunculopontine tegmental (Hong and Hikosaka, 2014) and the sensory (Overton et al., 2014) controls of dopamine activity, the sex-dependent diversity in dopamine systems (Gillies et al., 2014) and the links between circadian systems and dopamine systems (Mendoza and Challet, 2014) are reviewed. The functional antero-posterior heterogeneity of the ventral tegmental area (VTA) and the role of its GABA tail (tVTA) (Sanchez-Catalan et al., 2014), the functional heterogeneity of the VTA outputs (Walsh and Han, 2014), the different roles of the D1 and D2 pathways (Keeler et al., 2014, Nakanishi et al., 2014), the place of dopamine in cortico-basal ganglia circuitry (Haber, 2014) and its role in associative learning and memory (Puig et al., 2014), are also addressed.

Section snippets

Overview of the contributions to this special issue

The midbrain dopaminergic complex includes the VTA, the substantia nigra (SN) and the retrorubral field. The inputs and outputs of these brain regions are reviewed by Yetnikoff et al. (2014). After presenting the general organization of these regions, including the cellular diversity, the authors are detailing the afferent and efferent connections based on anatomo-functional categories. Species differences are discussed, as well as the complexity of the intrinsic organization and the network

Conclusion

The 17 contributions to this special issue provide interesting points of view on chosen topics, spanning molecular, cellular, electrophysiology, anatomy, circuit and behavioral aspects, and highlighting the heterogeneity of this brain region. However, they cannot pretend being exhaustive and covering all knowledge on the ventral tegmentum and on dopamine systems.

Part of the advances reviewed in this special issue was allowed by recent technical progress, mainly implemented in mice, such as cell

Acknowledgments

Supported by the Centre National de la Recherche Scientifique and by the Agence Nationale de la Recherche (ANR-11-bsv4-002).

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