NMDA receptor- and metabotropic glutamate receptor-dependent synaptic plasticity induced by high frequency stimulation in the rat dentate gyrus in vitro

1. The mechanisms of long-term potentiation (LTP) and long-term depression (LTD) induced by brief high frequency stimulation (HFS), paired with a part icular pattern and amplitude of depolarisation has been investigated in the medial perforant pathway of the dentate gyrus of the 2- to 3-week-old rat hippocampus in vitro. 2. N-Methyl-D-aspartate (NMDA) receptor (NMDAR) activation was measured qua ntitatively during HPS-induced NMDAR-dependent LTP, LTD and at the LTD-LTP crossover point in order to test the hypothesis that the induction of the p articular form of plasticity depends on the intensity of NMDAR activation. 3. The induction of LTD, the LTD-LTP crossover point and LTP was associated with an increasing NMDAR charge transfer. 4. In addition to the NMDAR-dependent LTD, a group I metabotropic glutamate receptor (mGluR)-dependent LTD could be induced by high intensity HFS pair ed with depolarisation under conditions of NMDAR inhibition. 5. The induction of mGluR-dependent LTD requires membrane depolarisation, C a2+ influx via L-type Ca2+ channels and a rise in intracellular Ca26. Quantal analysis involving minimal stimulation demonstrated that the mGl uR-dependent LTD induction was associated with a decrease in potency and an increase in failure rate.