Description: Midbrain dopaminergic neurons play a critical role in multiple brain functions, and abnormal signaling through dopaminergic pathways has been implicated in several major neurologic and psychiatric disorders. One well-studied target for the actions of dopamine is DARPP32. In the densely dopamine- and glutamate-innervated rat caudate-putamen, DARPP32 is expressed in medium-sized spiny neurons (Ouimet and Greengard, 1990) that also express dopamine D1 receptors (Walaas and Greengard, 1984). The function of DARPP32 seems to be regulated by receptor stimulation. Both dopaminergic and glutamatergic (NMDA) receptor stimulation regulate the extent of DARPP32 phosphorylation, but in opposite directions (Halpain et al., 1990). Dopamine D1 receptor stimulation enhances cAMP formation, resulting in the phosphorylation of DARPP32 (Walaas and Greengard, 1984); phosphorylated DARPP32 is a potent protein phosphatase-1 (see MIM 176875) inhibitor (Hemmings et al., 1984). NMDA receptor stimulation elevates intracellular calcium, which leads to activation of calcineurin and dephosphorylation of phospho-DARPP32, thereby reducing the phosphatase-1 inhibitory activity of DARPP32 (Halpain et al., 1990).[supplied by OMIM]