CA2+ CALMODULIN-DEPENDENT PROTEIN-KINASE-II PHOSPHORYLATION OF THE PRESYNAPTIC PROTEIN SYNAPSIN-I IS PERSISTENTLY INCREASED DURING LONG-TERM POTENTIATION/

Long-term potentiation (LTP) is an increase in synaptic responsiveness thought to be involved in mammalian learning and memory, The localiza tion (presynaptic and/or postsynaptic) of changes underlying LTP has b een difficult to resolve with current electrophysiological techniques. Using a biochemical approach, we have addressed this issue and attemp ted to identify specific molecular mechanisms that may underlie LTP. W e utilized a novel multiple-electrode stimulator to produce LTP in a s ubstantial portion of the synapses in a hippocampal CA1 minislice and tested the effects of such stimulation on the presynaptic protein syna psin I. LTP-inducing stimulation produced a long-lasting 6-fold increa se in the phosphorylation of synapsin I at its Ca2+/calmodulin-depende nt protein kinase II (CaM kinase II) sites without affecting synapsin I levels. This effect was fully blocked by either the N-methyl-D-aspar tate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (APV) or the CaM kinase II inhibitor KN-62, Our results indicate that LTP ex pression is accompanied by persistent changes in presynaptic phosphory lation, and specifically that presynaptic CaM kinase II activity and s ynapsin I phosphorylation may be involved in LTP expression.