ENDOGENOUS PROTEIN-KINASE-A INHIBITOR (PKI-ALPHA) MODULATES SYNAPTIC ACTIVITY

Protein kinase A (PKA) has long been known to be involved in major reg ulatory mechanisms underlying synaptic plasticity and complex behavior s such as learning and memory, The endogenous PKA inhibitor, PKI alpha , has been extensively studied for its effects on PKA and PKA-mediated signal transduction, Clear functions for PKI alpha in vivo, however, remain to be established, Here we describe that several forms of synap tic stimulation in the rat hippocampus cause a dramatic decrease in th e concentration of PKI alpha in dentate granule cells. Furthermore, ch ronic infusion of antisense oligonucleotides against PKI alpha into th e rat brain results in a dramatic reduction of the excitability of the se neurons and elimination of their ability to exhibit long-term poten tiation (LTP) and long-term depression (LTD), suggesting a stimulus-de pendent regulatory role for PKI alpha in PKA signal transduction, J, N eurosci, Res. 53:269-278, 1998, (C) 1998 Wiley-Liss, Inc.