Braking dopamine systems: a new GABA master structure for mesolimbic and nigrostriatal functions.

International audienceA new mesopontine structure exerting a strong influence on dopamine systems has recently been defined: the tail of the ventral tegmental area/rostromedial tegmental nucleus (tVTA/RMTg). This review presents a neuroanatomical, physiological, and behavioral overview of some of the recent and ongoing research on this brain region and its relationship with dopamine systems. The tVTA/RMTg sends dense GABA projections to VTA and substantia nigra neurons. The inhibitory influence of tVTA/RMTg on dopamine neurons is supported by both neuroanatomical and electrophysiology data. The latter studies also reveal the tVTA/RMTg as a substrate for morphine and cannabinoid action on dopamine cells. In primates, the tVTA/RMTg has been implicated in reward prediction error signals, through a basal ganglia-lateral habenula-tVTA/RMTg-dopamine-basal ganglia circuit. In rodents, the tVTA/RMTg has been shown to play a critical role in aversive behaviors, particularly those involving behavioral inhibition, such as freezing and avoidance. These findings highlight the functional importance of the tVTA/RMTg as a major GABA brake for dopamine systems

Control of the nigrostriatal dopamine neuron activity and motor function by the tail of the ventral tegmental area.

International audienceMidbrain 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