Inhibition of phosphatase 2B prevents expression of hippocampal long-term potentiation.

The induction of long-term potentiation (LTP) in the CA1 region of the hippocampus is mediated by N-methyl-D-aspartate (NMDA) receptor-coupled calcium influx. In addition, calcium/calmodulin (CaM) has been demonstrated to play an essential role in the induction process. In the present study, a possible role of CaM-dependent phosphatase (phosphatase 2B, PP-2B, calcineurin) in the LTP process was examined by intracellular recordings in apical dendrites of CA1 pyramidal cells of adult guinea-pigs. In dendrites in which cypermethrin, a potent and specific inhibitor of PP-2B (IC50 40 pM), was intracellularly applied, tetanization generated only short-term increases (15-30 min) of excitatory responses. In the intracellular presence of allethrin, a weak inhibitor of PP-2B, LTP expression was not affected. These findings demonstrate that activation of PP-2B is a necessary condition for the expression of LTP in CA1 pyramidal cell dendrites.