DIFFERENT MECHANISMS MAY BE REQUIRED FOR MAINTENANCE OF NIMDA RECEPTOR-DEPENDENT AND INDEPENDENT FORMS OF LONG-TERM POTENTIATION

In hippocampal area CA1, long-term potentiation (LTP) is induced by te tanic stimulation protocols that activate N-methyl-D-aspartate (NMDA) receptors. In addition, some stimulation protocols can induce LTP duri ng NMDA receptor blockade. An initial signal in both NMDA receptor-dep endent and independent LTPs is increased intracellular Ca2+ concentrat ion in postsynaptic neurons. It therefore seems possible that subseque nt steps leading to expression and maintenance of potentiation are sha red whether or not LTP is induced through NMDA receptor activation. We tested this hypothesis by applying a broad spectrum protein kinase in hibitor, previously shown to inhibit NMDA receptor-dependent LTP. In a greement with earlier reports, we found that H-7 inhibited NMDA recept or-dependent LTP when applied either during tetanic stimulation, or be ginning 30 min following tetanic stimulation. In contrast, NMDA recept or-independent LTP was not inhibited by H-7 applied during or followin g tetanic stimulation. We also tested for mutual occlusion between NMD A receptor-dependent and independent LTPs. Although induction of NMDA receptor-independent LTP did not occlude later induction of NMDA recep tor-dependent LTP, induction of NMDA receptor-dependent LTP did occlud e NMDA receptor-independent LTP. While the kinase inhibitor experiment showed a clear difference between NMDA receptor-dependent and indepen dent LTPs, the occlusion experiments suggest an interaction between th e signalling pathways for the two LTPs. (C) 1995 Wiley-Liss, Inc.