Calcineurin functions include (a) regulation of presynaptic phosphorylation of dynamin and the PP1 inhibitor DARPP-32, (b) postsynaptic phosphoregulation via actions from its anchored localization to scaffolding proteins in postsynaptic densities, and (c) regulation of transcriptional modulators that include the transcription factor NFAT (Yakel, 1997). Calcineurin plays roles in multiple brain circuits important for reward, memory, and aging in ways thought to link dopaminergic and glutamatergic signals (Gerber et al., 2003). Altered calcineurin expression or function can alter rewarding effects of abused substances (Biala, Betancur, Mansuy, & Giros, 2005; Gerdjikov and Beninger, 2005), alter long-term potentiation (LTP; Winder, Mansuy, Osman, Moallem, & Kandel, 1998) and change memory functions (Malleret et al., 2001; Mansuy, Mayford, Jacob, Kandel, & Bach, 1998). Evidence that directly implicates calcineurin in the memory-associated affliction, Alzheimer's disease (AD), include observations that overall calcineurin expression levels and calcineurin activities are reduced in AD brains (Gong, Liu, Grundke-Iqbal, & Iqbal, 2006). PPP3CA activity is reduced and its aggregation is increased in the aging brain (Agbas, Zaidi, & Michaelis, 2005).
