Hyperactive DA enhancement of D1-MSN excitability in the dorsal striatum (DS) in Pitx3Null mice. Pitx3Null mice have a gradient striatal DA denervation (Figure 1A,B) with the DA loss in the very dorsal DS being ~99% and the NAc DA loss being about 50% (weak to non-supersensitivity; hence, no DA receptor hyperfunctionality and no triggering of c-fos expression upon L-dopa stimulation [32]), resembling the DA loss pattern in PD patients and thus providing an outstanding opportunity for studying potentially gradient DA effects in parkinsonian striatum. The gene discussed is FOS; the disease is Parkinson disease.