Role of glycine receptors in the striatal network

The striatum is the largest nuclear complex of the basal ganglia (BG) associated with motor response where dopaminergic loops interact with local inhibitory GABAergic and cholinergic loops, facilitating or inhibiting simultaneously occurring neuronal signals. Whilst it was believed that the expression of Glycine receptors containing α2 (GlyRα2) subunit in the brain declines in adulthood, we have previously shown that besides GABA receptors, Medium Spiny Neurons (MSN), the projection neurons of the striatum, express functional chloride permeable GlyR, at adulthood, with α2 as the agonist binding subunit. We also showed that the depletion of GlyRα2 in global GlyRα2 knock-out mice leads to motor deficits, exaggerated response in reward motivated tasks and is associated with increased striatal signalling. However, neurodevelopmental impact and the separate roles of glycinergic currents in MSN expressing D1 or D2 receptor (dMSN and iMSN) in these GlyRα2-mediated phenotypes have not been explored. To rule out neurodevelopmental effects, we knocked-down GlyRα2 (cKD) in the adult striatum in a cell-type and region-specific manner. We also generated floxed-GlyRα2 conditional knock-out mice and crossed them with Drd1-Cre or A2Ar-Cre mice to obtain cell-type specific conditional knock-out (cKO) models. Acute slice electrophysiology was used to verify KO and KD models by studying the glycinergic currents. Preliminary characterisation of passive properties of the dMSN and iMSN was done in the cKO and cKD mice models. Altogether, our goal is to precisely characterize the role of glycinergic transmission in striatal relay function.