title: Control of the nigrostriatal dopamine neuron activity and motor function by the tail of the ventral tegmental area.
abstract: Midbrain dopamine neurons are implicated in various psychiatric and neurological disorders. The GABAergic tail of the ventral tegmental area (tVTA), also named the rostromedial tegmental nucleus (RMTg), displays dense projections to the midbrain and exerts electrophysiological control over dopamine cells of the VTA. However, the influence of the tVTA on the nigrostriatal pathway, from the substantia nigra pars compacta (SNc) to the dorsal striatum, and on related functions remains to be addressed. The present study highlights the role played by the tVTA as a GABA brake for the nigrostriatal system, demonstrating a critical influence over motor functions. Using neuroanatomical approaches with tract tracing and electron microscopy, we reveal the presence of a tVTA-SNc-dorsal striatum pathway. Using in vivo electrophysiology, we prove that the tVTA is a major inhibitory control center for SNc dopamine cells. Using behavioral approaches, we demonstrate that the tVTA controls rotation behavior, motor coordination, and motor skill learning. The motor enhancements observed after ablation of the tVTA are in this regard comparable with the performance-enhancing properties of amphetamine, a drug used in doping. These findings demonstrate that the tVTA is a major GABA brake for nigral dopamine systems and nigrostriatal functions, and they raise important questions about how the tVTA is integrated within the basal ganglia circuitry. They also warrant further research on the tVTA's role in motor and dopamine-related pathological contexts such as Parkinson's disease.
authors.affiliation: 1] Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, Strasbourg, France [2] Université de Strasbourg, Strasbourg, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Bourdy
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, Strasbourg, France.
authors.forename: María-José
authors.initials: MJ
authors.lastname: Sánchez-Catalán
authors.affiliation: 1] Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, Strasbourg, France [2] Centre National de la Recherche Scientifique, Interdisciplinary Institute for Neuroscience, Bordeaux, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kaufling
authors.affiliation: Department of Neuroscience and Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Judith J
authors.initials: JJ
authors.lastname: Balcita-Pedicino
authors.affiliation: 1] Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, Strasbourg, France [2] Université de Strasbourg, Strasbourg, France.
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Freund-Mercier
authors.affiliation: 1] Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, Strasbourg, France [2] Université de Strasbourg, Strasbourg, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Veinante
authors.affiliation: Department of Neuroscience and Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Sesack
authors.affiliation: 1] Centre National de la Recherche Scientifique, Interdisciplinary Institute for Neuroscience, Bordeaux, France [2] Université de Bordeaux, Interdisciplinary Institute for Neuroscience, Bordeaux, France.
authors.forename: François
authors.initials: F
authors.lastname: Georges
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, Strasbourg, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Barrot
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D007858:Learning / Q000502:physiology; D008297:Male; D008839:Microelectrodes; D008854:Microscopy, Electron; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D056347:Neuroanatomical Tract-Tracing Techniques; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D012399:Rotation; D013378:Substantia Nigra / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*
chemical_list: D000697:Central Nervous System Stimulants; D003913:Dextroamphetamine