LONG-TERM POTENTIATION REQUIRES ACTIVATION OF CALCIUM-INDEPENDENT PHOSPHOLIPASE A(2)

The predominant phospholipase activity present in rat hippocampus is a calcium-independent phospholipase A, (302.9 +/- 19.8 pmol/mg . min fo r calcium-independent phospholipase A(2) activity vs, 14.6 +/- 1.0 pmo l/mg . min for calcium-dependent phospholipase A(2) activity), This ca lcium-independent phospholipase A(2) is exquisitely sensitive to inhib ition by the mechanism-based inhibitor, omcthylene)-tetrahydro-3-(1-na phthalenyl)-2H-pyran -2-one (EEL), Moreover, treatment of hippocampal slices with EEL prior to tetanic stimulation prevents the induction of LTP (40.8 +/- 5.6% increase in excitatory postsynaptic potential (EPS P) slope for control slices (n = 6) vs, 5.8 +/- 8.5% increase in EPSP slope for EEL-treated slices (n = 8)), Importantly, LTP can be induced following mechanism-based inhibition of phospholipase A(2) by providi ng the end product of the phospholipase A(2) reaction, arachidonic aci d, during the application of tetanic stimulation, Furthermore, the ind uction of LTP after treatment Kith EEL is dependent on the stereoelect ronic configuration of the fatty acid provided since eicosa-5,8,11-tri enoic acid, but not eicosa-8,11,14-trienoic acid, rescues LTP after EE L treatment (37.6 +/- 16.1% increase in EPSP slope for eicosa-5,8,11-t rienoic acid vs, -3.7 +/- 5.2% increase in EPSP slope for eicosa-8,11, 14-trienoic acid). Collectively, these results provide the first demon stration of the essential role of calcium-independent phospholipase A( 2) in synaptic plasticity.