DEVELOPMENTAL ALTERATIONS IN THE SENSITIVITY OF HIPPOCAMPAL NMDA RECEPTORS TO AP5

Changes in the properties of the N-methyl-D-aspartate (NMDA) receptor are proposed as a factor in the decrease in synaptic plasticity during maturation of the brain. Alterations in the hippocampal NMDA receptor population were studied during development by comparing competitive a ntagonist efficacy during a window characterized by hyperexcitability and active synaptogenesis to that seen in a more mature period. A deve lopmental change in the sensitivity of the N-methyl-D-aspartate (NMDA) evoked response to the competitive antagonist D(-)2-amino-5-phosphono pentanoic acid (D-AP5) was observed by whole-cell mode voltage-clamp, intracellular and extracellular recordings in hippocampal slices. Thes e differences were observed in the portions of the hippocampus that co ntain the terminal axon arbors of the CA(3) pyramidal neurons, the syn aptic fields of the Schaffer collateral, associational and commissural pathways. The apparent antagonist efficacy was 2-3 times greater in i mmature slices obtained on postnatal day (PND) 10-16 than that observe d in more mature tissue (> PND38). Given the possible role of the NMDA receptor in network plasticity, these observations could indicate a r ole for the molecular diversity of this important receptor subtype fam ily in the maturation of hippocampal pathways.