POSTNATAL-DEVELOPMENT OF GLUTAMATE RECEPTOR-MEDIATED RESPONSES IN THENEOSTRIATUM

Three experimental approaches were used to examine the maturation of N -methyl-D-aspartate (NMDA) receptors in the neostriatum and compare th eir developmental profile to that of the non-NMDA receptors [alpha-ami no-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate (K A)]. The first, and least conventional approach utilized infrared vide omicroscopy to measure NMDA-induced swelling in single cells in a brai n slice. The results demonstrated that NMDA receptors display an incre mental 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 c ell swelling was proportionately greater than NMDA-induced cell swelli ng suggesting earlier maturation of this non-NMDA receptor subtype. Th e second approach used whole-cell patch clamp analysis to examine NMDA currents and compare their maturation to AMPA/ KA-iuduced currents. T hough the data are still preliminary, a very similar developmental pat tern emerged. NMDA-induced currents were small and developed slowly af ter PND 7. In contrast, AMPA/KA-induced currents were larger and appea red to develop earlier. Finally, dizocilpine (MK-801) binding was meas ured in homogenates of neostriatal tissue. The ontogeny of binding res embled 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 ad ult (PND 60). The affinity of MK-801 for the receptor did not change d uring 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 P ND 14. In contrast, neostriatal AMPA/KA receptor function appears to p recede NMDA receptor function.