Dopamine-mediated striatal activity and function is enhanced in GlyR alpha 2 knockout animals

Abstract

The glycine receptor alpha 2 (GlyR alpha 2) is a ligand-gated ion channel which upon activation induces a chloride conductance. Here, we investigated the role of GlyRa2 in dopamine-stimulated striatal cell activity and behavior. We show that depletion of GlyR alpha 2 enhances dopamine-induced increases in the activity of putative dopamine D1 receptor-expressing striatal projection neurons, but does not alter midbrain dopamine neuron activity. We next show that the locomotor response to d-amphetamine is enhanced in GlyRa2 knockout animals, and that this increase correlates with c-fos expression in the dorsal striatum. 3-Dmodeling revealed an increase in the neuronal ensemble size in the striatum in response to D-amphetamine in GlyR alpha 2 KO mice. Finally, we show enhanced appetitive conditioning in GlyR alpha 2 KO animals that is likely due to increased motivation, but not changes in associative learning or hedonic response. Taken together, we show that GlyR alpha 2 is an important regulator of dopamine-stimulated striatal activity and function.