Striatal interneuron changes in hemiparkinsonian and L-DOPAinduced dyskinetic mice

GOMEZ, GIMENA; BORDONE, MELINA; SANZ-BLASCO, SARA; FERRARIO, JUAN ESTEBAN; TARAVINI, IRENE; MURER, GUSTAVO; GERSHANIK, OSCAR

Mar del Plata

Congreso; XXX SAN Annual meeting; 2015

Sociedad Argentina de Investigaciones en Neurociencias

The administration of L-DOPA still remains as the preferred treatment for Parkinson´s disease despite its propensity to induce severe motor complications, known as L-DOPAinduced dyskinesias (LID). Striatal interneurons strongly modulate striatal output, and changes in striatal microcircuits may contribute to basal ganglia dysfunction in a number of movement disorders.We determined changes in number and activity of the different populations of striatal interneurons in a mouse model of hemiparkinsonism and L-DOPA induced dyskinesias. C57BL6 mice were injected with 6-hydroxydopamine (6-OHDA) or vehicle in the medial forebrain bundle and treated daily with a dyskinetogenic dose of L-DOPA or saline solution. 6-OHDA lesion led to changes in the number of parvalbumin (PV) + and calretinin (CR) + interneurons. CR+ but not PV+ cell density returned to normal levels after L-DOPA treatment. No change was observed in cholinergic or somatostatin (SST)+ interneurons. 6-OHDA lesion led to an increased c-fos expression which was further increased after L-DOPA treatment. While no PV+ nor CR+ interneurons showed c-fos expression in any condition,~47% of SST+ and ~7% of cholinergic interneurons where c-fos positive in LID but not in 6-OHDA animals. Our findings suggest that changes in striatal interneurons contribute to the maladaptive state that occurs after dopamine depletion. In addition, chronic treatment with L-DOPA fails to reestablish the initial physiological landscape.