Direct Evaluation of L-DOPA Actions on Neuronal Activity of Parkinsonian TissueIn Vitro

Abstract

Physiological and biochemical experimentsin vivoandin vitrohave explored striatal receptor signaling and neuronal excitability to posit pathophysiological models of Parkinson's disease. However, when therapeutic approaches, such as dopamine agonists, need to be evaluated, behavioral tests using animal models of Parkinson's disease are employed. To our knowledge, recordings of population neuronal activityin vitroto assess anti-Parkinsonian drugs and the correlation of circuit dynamics with disease state have only recently been attempted. We have shown that Parkinsonian pathological activity of neuronal striatal circuits can be characterized inin vitrocerebral tissue. Here, we show that calcium imaging techniques, capable of recording dozens of neurons simultaneously with single-cell resolution, can be extended to assess the action of therapeutic drugs. We used L-DOPA as a prototypical anti-Parkinsonian drug to show the efficiency of this proposed bioassay. In a rodent model of early Parkinson's disease, Parkinsonian neuronal activity can be returned to control levels by the bath addition of L-DOPA in a reversible way. This result raises the possibility to use calcium imaging techniques to measure, quantitatively, the actions of anti-Parkinsonian drugs over time and to obtain correlations with disease evolution and behavior.