Developmental regulation of NMDA receptor 2B subunit mRNA and ifenprodil binding in the zebra finch anterior forebrain

In passerine songbirds, song learning often is restricted to an early sensi tive period and requires the participation of several discrete regions with in the anterior forebrain, Activation of N-methyl-D-aspartate (NMDA) recept ors is implicated in song learning and in one forebrain song region, the la teral magnocellular nucleus of the anterior neostriatum (IMAN), Nn LDA rece ptors decrease in density, their affinity for the antagonist MK-801 increas es, and their currents decay more quickly as young male zebra finches lose the ability to imitate new song elements, These developmental changes in NM DA receptor pharmacology and physiology suggest that the subunit compositio n of NMDA receptors changes developmentally. Here, me have used in situ hyb ridization and [H-3]ifenprodil receptor autoradiography to study the develo pmental regulation of the NMDA receptor 2B subunit (NR2B) within the anteri or forebrain of male zebra finches, NR2B mRNA expression within the IMAN wa s twice as great in 30-day-old males (early in the sensitive period for son g learning) as in adult males, and this developmental decrease in NR2B mRNA expression was mirrored by a decrease in high-affinity (NR2B-associated) [ H-3]ifenprodil binding within this song region. In another anterior forebra in song region, Area;X, NR2B mRNA also declined significantly after 30 days posthatch, but this decline was not accompanied by a significant decrease in [H-3]ifenprodil binding. The results are consistent with the hypothesis that developmental changes in NMDA receptor function mediated by regulation of subunit composition contribute to the sensitive period for vocal learni ng in birds. (C) 1999 John Wiley &: Sons, Inc.