Control of dopaminergic systems through the GABAergic tail of the ventral tegmental area – tVTA-DA

To reach the project's objectives, the partners will combine neuroanatomical, electrophysiological and behavioral approaches in rodents. The neuroanatomical approaches allow visualizing the neuronal circuits and the synapses. The electrophysiological approaches allow recording neuronal activity. The behavioral approaches allow the study of functions that are controlled by the tVTA.

The tVTA-DA project brings valuable information on the controls that the tVTA exerts on neurons from the ventral tegmental area and the substantia nigra and on the behavioral functions of the nigrostriatal pathway. The results support the hypothesis that the tVTA is a main inhibitory control center for mesolimbic and nigrostriatal pathways.

Data from the tVTA-DA project will offer major advances in our knowledge of this new brain region and of the controls of dopaminergic systems. This progress may open the way to preclinical and clinical researches on the possible implication of the tVTA in neurological and psychiatric pathologies associated with dopamine systems.

Barrot M, Sesack SR, Georges F, Pistis M, Hong S, Jhou TC (2012) Braking dopamine systems: a new GABA master structure for mesolimbic and nigrostriatal functions. J Neurosci 32:14094-14101.

Newly discovered brain structures may help to improve our knowledge of brain functions and of brain disorders, and may provide new neuroanatomical targets for treatments. The present project concerns a recently described brain region, the tail of the ventral tegmental area (tVTA), which may be a major inhibitory control center for the dopaminergic systems.
The main dopaminergic systems arise from midbrain areas harboring dopamine neurons cell bodies and projecting to a wide array of brain structures where they exert a critical modulatory influence. The mesolimbic system from the ventral tegmental area (VTA) to the nucleus accumbens and prefrontal cortex, and the nigrostriatal system from the substantia nigra pars compacta (SNc) to the striatum, are the most studied of them. They influence numerous physiological functions and are implicated in the etiology or treatment of neurological or psychiatric diseases, such as Parkinson’s, schizophrenia, mood disorders, and drug abuse. A growing body of experimental data supports the view that elucidating the electrophysiological functioning of dopamine neurons may be helpful to understand brain mechanisms underlying the pathogenesis of these neurological and mental disorders. Our project participates to this effort by providing valuable knowledge on the control of dopaminergic system activity.
With the hypothesis that tVTA may be a critical inhibitory control center for dopaminergic systems, the tVTA-DA project gathers 3 academic partners and is developed around 2 objectives: first to characterize tVTA influence on VTA neurons and second to characterize tVTA influence on the nigrostriatal pathway.
To reach these objectives, the partners will combine neuroanatomical, in vivo electrophysiological and behavioral approaches in rats. The neuroanatomical studies will use single-neuron reconstruction of projections and terminal fields, combined tract-tracing visualization of circuits and electron microscopy analysis of synapses. The electrophysiological studies will use in vivo single unit recordings on anesthetized animals to characterize tVTA influence on VTA and SNc neurons. The behavioral studies will use lesional approaches to characterize tVTA influence over locomotor and motor coordination functions. Partners expertise, solid preliminary results, and the scientific program should ensure the project success.
The tVTA-DA project will bring valuable informations on tVTA control of VTA and SNc neurons, and will offer the first evaluation of tVTA influence over functions controlled by the nigrostriatal pathway. It will thus constitute a major step in our understanding of this new brain region and of the control of dopaminergic systems activity.