Control of the nigrostriatal dopamine neuron activity and motor function by the tail of the ventral tegmental area.
Neuropsychopharmacol. 2014-06-04; 39(12): 2788-2798
DOI: 10.1038/npp.2014.129
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1. Neuropsychopharmacology. 2014 Nov;39(12):2788-98. doi: 10.1038/npp.2014.129. Epub
2014 Jun 4.
Control of the nigrostriatal dopamine neuron activity and motor function by the
tail of the ventral tegmental area.
Bourdy R(1), Sánchez-Catalán MJ(2), Kaufling J(3), Balcita-Pedicino JJ(4),
Freund-Mercier MJ(1), Veinante P(1), Sesack SR(4), Georges F(5), Barrot M(2).
Author information:
(1)1] Institut des Neurosciences Cellulaires et Intégratives, Centre National de
la Recherche Scientifique, Strasbourg, France [2] Université de Strasbourg,
Strasbourg, France.
(2)Institut des Neurosciences Cellulaires et Intégratives, Centre National de la
Recherche Scientifique, Strasbourg, France.
(3)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.
(4)Department of Neuroscience and Department of Psychiatry, University of
Pittsburgh, Pittsburgh, Pennsylvania, USA.
(5)1] Centre National de la Recherche Scientifique, Interdisciplinary Institute
for Neuroscience, Bordeaux, France [2] Université de Bordeaux, Interdisciplinary
Institute for Neuroscience, Bordeaux, France.
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.
DOI: 10.1038/npp.2014.129
PMCID: PMC4200489
PMID: 24896615 [Indexed for MEDLINE]