Dopamine-mediated striatal activity and function is enhanced in GlyRa2 knockout animals

Abstract

The glycine receptor alpha 2 (GlyRa2) 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 GlyRa2 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-D modeling revealed an increase in the neuronal ensemble size in the striatum in response to D-amphetamine in GlyRa2 KO mice. Finally, we show enhanced appetitive conditioning in GlyRa2 KO animals that is likely due to increased motivation, but not changes in associative learning or hedonic response. Taken together, we show that GlyRa2 is an important regulator of dopamine-stimulated striatal activity and function.