Evaluation of neural connectivity between parvalbuminexpressing interneurons and medium spiny neurons in the lesioned striatum of dyskinetic mice.

TARAVINI IR; GOMEZ G; ESCANDE M; MURER MG; GERSHANIK OS

San Diego, California

Congreso; 19 th International Congress of Parkinson´s Disease and Movement Disorders; 2015

International Parkinson´s Disease and Movement Disorders Society

Objective: To establish whether the development of dyskinesias induced by L-DOPA modifies the connectivity of parvalbumin-expressing interneurons with medium spiny neurons in the lesioned striatum of transgenic mice expressing fluorescent proteins under the control of the D1 and D2 receptor promoter.Background:Dyskinesias are a debilitating side-effect of chronic L-DOPA administration, despite of which, the drug remains as the gold standard for symptomatic treatment of Parkinson´s disease (PD). Abnormal stimulation of dopaminergic receptors byL-DOPA correlates with long-term functional synaptic changes in striatal medium spiny neurons (MSNs) deprived of dopaminergic innervations which may contribute to the development of dyskinesias (LID). Parvalbumin striatal interneurons modulate and control differentially the activity of MSNs expressing either D1 or D2 receptors and therefore contributing to the imbalance between these pathways both in PD and LID. However, the state of the connectivity between these cell populations in the dyskinetic condition remains elusive.Methods: Transgenic mice expressing red (tomato) or green (EGFP) fluorescent markers in striatal neurons containing either the D1 or D2 receptor promoter were lesioned unilaterally with 6-OHDA in the mfb and treated with L-DOPA to induce severe dyskinesias. Parvalbumin was determined by inmunofluorescence on fixed striatal tissue sections using Cy5 as fluorochrome. The number of synaptic contacts of parvalbumin positive terminals on D1 or D2 MSNs was quantified on confocal microphotograph using the ImageJ software (NIH).Results: Lesioned mice developed severe dyskinesias after L-DOPA administration. Preliminary results show that the number of perisomaticparvalbumin synapses on D1 and D2 MSNs remains unaltered after 6-OHDA lesion. Conversely, a dyskinetogenic dose of L-DOPA reduces the number of parvalbumin contacts onto D2 but not D1 MSNs.Conclusions: These results suggest that L-DOPA affects the synaptic connectivity of parvalbumin interneurons with both types of MSNs differentially. These are clear evidences that L-DOPA treatment induces alterations at structural and functional levels that lead to a new pathophysiologic condition in the basal ganglia circuits. Further analysis will help to clarify if these structural adaptations are directly related to the development of dyskinesias.