Postnatal Development of Glutamate Receptor-Mediated Responses in the Neostriatum

Three experimental approaches were used to examine the maturation of N-methyl-D-aspartate (NMDA) receptors in the neostriatum and compare their developmental profile to that of the non-NMDA receptors [α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate (KA)]. The first, and least conventional approach utilized infrared videomicroscopy to measure NMDA-induced swelling in single cells in a brain slice. The results demonstrated that NMDA receptors display an incremental pattern of postnatal development with no responses at postnatal day (PND) 3, weak responses at PND 7, the largest responses by PND 14 and slight decreases at PNDs 21 and 28. At PNDs 3 and 7, KA-induced cell swelling was proportionately greater than NMDA-induced cell swelling suggesting earlier maturation of this non-NMDA receptor subtype. The second approach used whole-cell patch clamp analysis to examine NMDA currents and compare their maturation to AMPA/KA-induced currents. Though the data are still preliminary, a very similar developmental pattern emerged. NMDA-induced currents were small and developed slowly after PND 7. In contrast, AMPA/KA-induced currents were larger and appeared to develop earlier. Finally, dizocilpine (MK-801) binding was measured in homogenates of neostriatal tissue. The ontogeny of binding resembled a step function with increases between PNDs 3 and 7 and PNDs 14 and 21. Binding peaked at PND 28 and then declined slightly in the adult (PND 60). The affinity of MK-801 for the receptor did not change during postnatal development. These findings demonstrate the pattern of functional development of glutamate receptors in the neostriatum. The NMDA receptor subtype displays minimal functional development until PND 14. In contrast, neostriatal AMPA/KA receptor function appears to precede NMDA receptor function.