Global long-term potentiation (LTP) was induced in organotypic hippocampal slice cultures by a brief application of 10 mM glycine. Glycine-induced LTP was occluded by previous theta burst stimulation-induced potentiation, indicating that both phenomena share similar cellular processes. Glycine-induced LTP was associated with increased Long-term potentiation (LTP) is an attractive candidate for a cellular mechanism of learning and memory as it exhibits many features expected for such a mechanism. It is induced by patterns of stimulation similar to those found in animals exploring novel environments; it is very long lasting (weeks in chronic preparations), and its pharmacology matches that of learning and memory (1, 2). It is generally agreed that LTP induction requires N-methyl-D-aspartate (NMDA) receptor activation, resulting in increase in postsynaptic calcium concentration and in the activation of several biochemical cascades leading to increased synaptic efficacy (3, 4). Possible mechanisms for LTP expression, in particular whether LTP is expressed as an increase in neurotransmitter release or by modifications of postsynaptic elements, are still a matter of debate (5-7). Over the last 10-15 years, a large body of evidence has been accumulated supporting the hypothesis that LTP expression is due, at least in part, to selective modifications of postsynaptic glutamate ␣-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.In the dentate gyrus of animals sacrificed 1 hr after LTP induction in the perforant path, the degree of LTP was positively correlated with increased [ 3 H]AMPA binding in the molecular layer (8). Allosteric effectors that increase AMPA receptor-mediated responses produced smaller increases in AMPA receptor-mediated responses after LTP induction (9, 10). Finally, the waveform of excitatory postsynaptic potentials (EPSPs) exhibited modifications consistent with a modification of AMPA receptor kinetics (11). Recent evidence suggests the existence in the hippocampus of a population of silent synapses, i.e., synapses that express NMDA receptor-mediated responses but no AMPA receptor-mediated responses (12, 13). After LTP induction, silent synapses were transformed into active synapses expressing functional AMPA receptors. The existence of such synapses could not only account for the controversial results and interpretations obtained from quantal analysis performed before and after LTP induction by several groups (14-16), but is also consistent with the idea that LTP is due, at least in part, to the transformation of nonfunctional AMPA receptors into functional receptors, an idea first proposed by Lynch and Baudry (17, 18).Although the above-discussed results implicate postsynaptic AMPA receptor modifications as part of the mechanisms underlying LTP expression, the nature of the changes as well as of the processes responsible for them are still unknown. A large body of work supports a critical role for the calciumdependent protease, calpain, in LTP induction. Calpain inhibito...
