Validation of a transgenic mouse line with knockdown of mGluR5 selectively in dopamine D1receptor expressing neurons

Abstract: One of the main difficulties of addiction treatment is the high risk of relapse even after a longabstinence and fully detoxification. Therefore, discovering the underlying molecular principlesof relapse is essential. The metabotropic glutamate receptor, mGluR5, is considered to beinvolved in this aspect. One of the brain structures expressing mGluR5 is the striatum, an areawith well-established role in addiction which is largely composed of medium-sized spinyneurons (MSNs). These neurons are basically divided into two major subpopulationscharacterized based on their projections and protein properties. It is known that the mGluR5receptor is expressed on both subpopulations of MSNs. Consequently, it can be used to establishthe proportional contribution of each of MSNs subpopulations in relapse to addiction. In ourconstellation, we have generated a mouse line designed to have a selective mGluR5 knock-downin one of these subpopulations – the dopamine D1 receptor (D1R) expressing neurons. It hashowever been unclear if the expression of the transgene is indeed limited to only D1R-expressingneurons. By immunofluorescence technique, I here show that the construct is expressed only inMSNs and is restricted to the D1R-expressing cell population in the striatum. Thus the transgenicmouse line is a good tool for the study of mGluR5 selectively in D1R expressing neurons.