These data indicate that PDE9A inhibition can be effective for increasing responsiveness of MSNs to cortical drive in both the intact and diseased HD striatum, however, the underlying mechanism leading to the observed facilitation may be different (i.e., presynaptic vs. postsynaptic effects, or direct effects on corticostriatal glutamatergic drive at the level of the cortex). The gene discussed is PDE9A; the disease is Huntington disease.