Analysis of the striatal fast-spiking interneurons contribution to the development of L-DOPA-induced dyskinesias.

GÓMEZ G; TARAVINI I; RELA L; BELFORTE J; MURER G; GERSHANIK O

Córdoba

Congreso; XXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias.; 2012

Sociedad Argentina de Investigación en Neurociencias.

L-DOPA-induced dyskinesias (LID) are the more common and incapacitatingcomplication of Parkinson’s disease therapy. LID are related to sensitization ofa D1R signalling cascade in striatal neurons deprived of dopaminergicinnervation and are rarely reversible. Previous studies revealed LID-relatedmorphological alterations in striatal projection neurons but the possible role ofthe interneurons has only been recently considered. Although the striatal fastspikingGABAergic interneurons (FSI) constitute only 2% of striatal cells, currentstudies indicate that they play an important role in the control of striatalexcitation-inhibition balance. Our current hypothesis is that chronicadministration of L-DOPA induces a diminution of FSI synaptic connectivity toD1 direct-pathway neurons, which results in a higher striatal output and thedevelopment of LID. To test it, we will develop an animal model of LID intransgenic mice expressing fluorescent proteins in FSI and D1R striatalneurons. We will study the number of FSI, their dendritic morphology and theconnectivity between FSI and D1R striatal projection neurons. Furthermore, wewill determine if FSI express the immediately early genes associated with thedevelopment of LID by means of immunohistochemistry. We expect that thiswork will provide innovative knowledge about the changes that take place in thestriatum after L-DOPA treatment and its relation with the development ofdyskinesias.