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Vincent Seutin

Midbrain dopaminergic neurons : from mechanisms of pacemaking ex vivo to firing properties in awake rats

Our laboratory is interested in the mechanisms controlling the electrical activity of midbrain dopaminergic (DA) neurons. The mechanism of slow pacemaking of these neurons ex vivo is rather controversial, in part because of methodological reasons and we have been addressing some of the current issues by combining various experimental approaches and modeling. This is not a trivial question since some authors believe that a major contribution of L-type Ca2+ channels to the pacemaking of nigral DA neurons may explain their propensity to neurodegeneration. We strongly believe that a complete description of the ion channel topography in these neurons will be critical to make progress in this area. Of course, slice physiology will not be able to explain the regulation of these neurons during behavioral tasks and we have therefore invested much time in developing telemetric recordings of ventral tegmental area neurons in freely moving rats. Our first study demonstrated that the reactivity of the DA system to passive cocaine administration is very different in anaesthetized and awake animals, suggesting that the "electrophysiological pharmacodynamics" of many agents on these neurons will need to be revisited in the latter condition. Current results and projects in this area will be presented.