Decreased protein phosphatase 2A activity in hippocampal long-term potentiation

Using autophosphorylated Ca2+/calmodulin-dependent protein kinase II (CaM k inase II) as substrate, we now find that long-term potentian (LTP) inductio n and maintenance are also associated with a significant decrease in calycu lin A-sensitive protein phosphatase (protein phosphatase 2A) activity, with out changes in Mg2+-dependent protein phosphatase (protein phosphatase 2C) activity. This decrease in protein phosphatase 2A activity was prevented wh en LTP induction was inhibited by treatment with calmidazolium or D-2-amino -5-phosphonopentanoic acid. In addition, the application of high-frequency stimulation to P-32-labeled hippocampal slices resulted in increases in the phosphorylation of a 55-kDa protein immunoprecipitated with anti-phosphata se 2A antibodies. Use of a specific antibody revealed that the 55-kDa prote in is the B'alpha subunit of protein phosphatase 2A, Following purification of brain protein phosphatase 2A, the Bla: subunit was phosphorylated by Ca M kinase Il,:an event that led to the reduction of protein phosphatase 2A a ctivity. These results suggest that the decreased activity in protein phosp hatase 2A following LTP induction contributes to the maintenance of constit utively active CaM kinase II and to the long-lasting increase in phosphoryl ation of synaptic components implicated in LTP.