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 antagonist efficacy during a window characterized by hyperexcitability and active synaptogenesis to that seen in a more mature period. A developmental change in the sensitivity of the N-methyl-D-aspartate (NMDA) evoked response to the competitive antagonist D(-)2-amino-5- phosphonopentanoic acid (D-AP5) was observed by whole-cell mode voltage-clamp, intracellular and extracellular recordings in hippocampal slices. These differences were observed in the portions of the hippocampus that contain the terminal axon arbors of the CA3 pyramidal neurons, the synaptic fields of the Schaffer collateral, associational and commissural pathways. The apparent antagonist efficacy was 2-3 times greater in immature slices obtained on postnatal day (PND) 10-16 than that observed in more mature tissue (> PND38). Given the possible role of the NMDA receptor in network plasticity, these observations could indicate a role for the molecular diversity of this important receptor subtype family in the maturation of hippocampal pathways.