POSTSYNAPTIC INHIBITORS OF CALCIUM CALMODULIN-DEPENDENT PROTEIN-KINASE TYPE-II BLOCK INDUCTION BUT NOT MAINTENANCE OF PAIRING-INDUCED LONG-TERM POTENTIATION/

The role of postsynaptic kinases in the induction and maintenance of l ong-term potentiation (LTP) was studied in the CA1 region of the rat h ippocampal slice. A peptide inhibitor for the catalytic domain of calc ium/calmodulin-dependent protein kinase type II (CaM-kinase) was appli ed through a perfused patch pipette. The inhibitor completely blocked bath the shortterm potentiation and LTP induced by a pairing protocol. This indicates that the kinase or kinases affected by the peptide are downstream from depolarization in the LTP cascade. The ability to blo ck LTP required that measures be taken to interfere with degradation o f the peptide kinase inhibitor by endogenous proteases; either additio n of protease inhibitors or modifications of the peptide itself greatl y enhanced the effectiveness of the peptide. Protease inhibitors by th emselves or control peptide did not block LTP induction. To study the effect of kinase inhibitor on LTP maintenance, we induced LTP in one p athway. Subsequent introduction of the kinase inhibitor blocked the in duction of LTP in a second pathway, but it did not affect maintenance of LTP in the first. The implications for the role or kinases in LTP m aintenance are discussed.