State of the Art in Sub-Phenotyping Midbrain Dopamine Neurons

Author:

Basso Valentina1ORCID,Döbrössy Máté D.234ORCID,Thompson Lachlan H.56,Kirik Deniz7,Fuller Heidi R.89ORCID,Gates Monte A.1

Affiliation:

1. School of Medicine, Keele University, Staffordshire ST5 5BG, UK

2. Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional, Neurosurgery, Medical Center, University of Freiburg, 79106 Freiburg im Breisgau, Germany

3. Department of Stereotactic and Functional Neurosurgery, Medical Center, University of Freiburg, 79106 Freiburg im Breisgau, Germany

4. Faculty of Biology, University of Freiburg, 79104 Freiburg im Breisgau, Germany

5. Charles Perkins Centre, Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, Australia

6. Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA

7. Brain Repair and Imaging in Neural Systems (B.R.A.I.N.S) Unit, Department of Experimental Medical Science, Lund University, BMC D11, 22184 Lund, Sweden

8. School of Pharmacy and Bioengineering, Keele University, Staffordshire ST5 5BG, UK

9. Wolfson Centre for Inherited Neuromuscular Disease, TORCH Building, RJAH Orthopaedic Hospital, Oswestry SY10 7AG, UK

Abstract

Dopaminergic neurons in the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNpc) comprise around 75% of all dopaminergic neurons in the human brain. While both groups of dopaminergic neurons are in close proximity in the midbrain and partially overlap, development, function, and impairments in these two classes of neurons are highly diverse. The molecular and cellular mechanisms underlying these differences are not yet fully understood, but research over the past decade has highlighted the need to differentiate between these two classes of dopaminergic neurons during their development and in the mature brain. This differentiation is crucial not only for understanding fundamental circuitry formation in the brain but also for developing therapies targeted to specific dopaminergic neuron classes without affecting others. In this review, we summarize the state of the art in our understanding of the differences between the dopaminergic neurons of the VTA and the SNpc, such as anatomy, structure, morphology, output and input, electrophysiology, development, and disorders, and discuss the current technologies and methods available for studying these two classes of dopaminergic neurons, highlighting their advantages, limitations, and the necessary improvements required to achieve more-precise therapeutic interventions.

Funder

Leverhulme Trust

Publisher

MDPI AG

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