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-coupl ed calcium influx. In addition, calcium/calmodulin (CaM) has been demo nstrated to play an essential role in the induction process. In the pr esent study, a possible role of CaM-dependent phosphatase (phosphatase 2B, PP-2B, calcineurin) in the LTP process was examined by intracellu lar recordings in apical dendrites of CAI pyramidal cells of adult gui nea-pigs. In dendrites in which cypermethrin, a potent and specific in hibitor of PP-2B (IC50 40 pM), was intracellularly applied, tetanizati on generated only short-term increases (15-30 min) of excitatory respo nses. In the intracellular presence of allethrin, a weak inhibitor of PP-2B, LTP expression was not affected. These findings demonstrate tha t activation of PP-2B is a necessary condition for the expression of L TP in CA1 pyramidal cell dendrites.