SAN2020

Action selection relies on the coordinated activity of striatal direct and indirect pathways, strongly modulated by dopamine (DA) and cholinergic neurons. Loss of mesencephalic DA neurons in Parkinson’s disease (PD) is thought to disrupt the balance between these modulators resulting in an alteration of basal ganglia circuits and motor disabilities. Striatal non cholinergic interneurons also play key roles in modulating striatal projection neurons, but their potential contribution to motor symptoms of PD is poorly understood. The goal of this project is to identify the role of striatal somatostatinergic interneurons (iSOM+) in the expression of motor deficits and the development of L-dopa-induced dyskinesias (LID). To this aim, we use Som-Cre mice unilaterally lesioned with 6-OHDA as a model of PD and evaluate behavioral performance while modulating iSOM+ activity using chemogenetic tools. As a first approach, we delivered a viral vector that directs the expression of an inhibitory DREADD in iSOM+, unilaterally into the striatum, and evaluated motor deficits by using three behavioral assays in the presence and absence of its synthetic ligand. Subsequently, mice were treated with increasing doses of L-dopa and we evaluated whether LID expression is altered by iSOM+ inhibition. Preliminary results showed that after L-dopa treatment (6 mg/kg), inhibition of iSOM+ increased LID expression , while no effects were found on basal locomotion nor on the development of motor deficits.