BIPHASIC CHANGES IN THE LEVELS OF N-METHYL-D-ASPARTATE RECEPTOR-2 SUBUNITS CORRELATE WITH THE INDUCTION AND PERSISTENCE OF LONG-TERM POTENTIATION

N-Methyl-D-aspartate glutamate receptors (NMDAR) form ion channels mad e up of polypeptides from two classes of subunits; NR1 is obligatory f or function whereas members of the NR2 class regulate the properties o f the channel. Long-term potentiation (LTP) of synaptic transmission i s an event largely dependent on NMDAR activation, and is studied as th e primary cellular model of memory in the mammalian brain. While there has been a focus on non-NMDARs in mediating the expression of LTP, we report here biochemical evidence for plasticity of the NMDAR that is associated with LTP persistence in awake animals. Following the establ ishment of LTP in perforant path synapses of the dentate gyrus, we obs erved a rise in NR2B protein levels 48 h post-tetanus which was depend ent upon activation of NMDARs during the tetanization, and which stron gly correlated with the degree of LTP measured at this time-point. We also observed a transient increase in both NR2B and NR2A protein level s 20 min post-tetanus that returned to control levels by 4 h. These ea rly increases were not observed in anaesthetized animals which do not sustain persistent LTP, Our data demonstrate a marked plasticity of NM DAR subunit expression, which may affect LTP persistence, as well as t he subsequent ability to induce LTP at previously activated synapses. (C) 1998 Elsevier Science B.V. All rights reserved.