This chapter concentrates on the basic mechanisms that are thought to underlie induction and expression of long-term plasticity (LTP). LTP has been demonstrated at all of the major synapses in the hippocampus. Activity-dependent LTP is a commonly observed feature of the neocortex and does not differ from the hippocampus in its induction or expression mechanisms. The induction and/or the magnitude of LTP and long-term depression (LTD) can be affected by prior activity that in itself does not produce observable changes in synaptic efficacy. Thus there is some plastic change of a different, or meta, form that influences traditional synaptic plasticity. N-methyl-D-aspartate receptors (NMDAR)-mediated synaptic transmission can undergo potentiation and depression, and given the critical role for NMDARs in LTP and LTD induction it is apparent that any change in NMDAR synaptic transmission brought about by a priming stimulus could have dramatic consequences for induction of LTP and LTD.