Proactive and retrograde effects on LTP produced by theta pulse stimulation: mechanisms and characteristics of LTP reversal in vitro.

Previous studies have established that (1) a 1-min episode of theta pulse stimulation (TPS) is sufficient to reverse potentiation during the early phases of LTP in area CA1 without causing depression when administered to nonpotentiated pathways; (2) the magnitude of depotentiation is inversely related to the delay between LTP induction and reversal attempts; and (3) pharmacological facilitation of AMPA receptor-mediated currents significantly enhances the strength of the reversal mechanism. The present experiments confirm and extend these results by showing that the depotentiating action of TPS on prior LTP is antagonized by inhibitors of protein phosphatases and adenosine A1 receptors but is not affected by NMDA receptor blockade, and, moreover, that TPS interferes with subsequent LTP induction by triggering an inhibitory mechanism that is active for a few minutes and is blocked by phosphatase inhibition. The possible implications of these results are discussed.