G9a influences neuronal subtype specification in striatum

Changes in brain gene expression by cocaine are known to involve epigenetic machineries. The histone methyltransferase G9a is a mediator of cocaine-induced structural and behavioral plasticity in the nucleus accumbens of mouse. This study finds cocaine-induced, G9a-mediated gene repression in both direct and indirect pathway medium spiny neurons (MSNs). The study also uses cell type–specific overexpression and conditional knockout of G9a in each MSN cell type and shows that G9a influences the developmental specification of striatal MSN subtypes, which in turn affects behavioral response to cocaine.