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

Abstract

In passerine songbirds, song learning often is restricted to an early sensitive period and requires the participation of several discrete regions within the anterior forebrain. Activation of N‐methyl‐D‐aspartate (NMDA) receptors is implicated in song learning and in one forebrain song region, the lateral magnocellular nucleus of the anterior neostriatum (lMAN), NMDA receptors decrease in density, their affinity for the antagonist MK‐801 increases, and their currents decay more quickly as young male zebra finches lose the ability to imitate new song elements. These developmental changes in NMDA receptor pharmacology and physiology suggest that the subunit composition of NMDA receptors changes developmentally. Here, we have used in situ hybridization and [3H]ifenprodil receptor autoradiography to study the developmental regulation of the NMDA receptor 2B subunit (NR2B) within the anterior forebrain of male zebra finches. NR2B mRNA expression within the lMAN was twice as great in 30‐day‐old males (early in the sensitive period for song learning) as in adult males, and this developmental decrease in NR2B mRNA expression was mirrored by a decrease in high‐affinity (NR2B‐associated) [3H]ifenprodil binding within this song region. In another anterior forebrain song region, Area X, NR2B mRNA also declined significantly after 30 days posthatch, but this decline was not accompanied by a significant decrease in [3H]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 learning in birds. © 1999 John Wiley & Sons, Inc. J Neurobiol 39: 155–167, 1999

Early sensory and hormonal experience modulate age-related changes in NR2B mRNA within a forebrain region controlling avian vocal learning

“…First, the decline in NR1 mRNA within the lMAN mirrors a decline in NMDAR density with both being particularly pronounced prior to PHD60 (Aamodt et al, 1995). Also, it has been shown previously that the developmental decline in NR2B mRNA within lMAN coincides with a decline in NR2B protein as measured by ifenprodil binding (Basham et al, 1999). Beyond these quantitative changes in NMDARs, it is likely that the regulation of NR2B transcript levels also produces qualitative changes in receptor phenotype.…”

“…In the mammalian visual system, NR2B:2A ratios decline and NMDAR-EPSCs shorten during the sensitive period, and dark-rearing delays these changes (Carmignoto and Vicini, 1992;Quinlan et al, 1999). Within the lMAN of songbirds, NR2B mRNA and protein expression decrease during song learning (Basham et al, 1999) as does the duration of NMDAR-EPSCs (Livingston and Mooney, 1997). In the present study, we provide the first demonstration that experimental manipulations that alter the timing and/or pace of song learning also affect age-related changes in NR2B (but not NR1) mRNA expression within the lMAN.…”

Overexpression of human NR2B receptor subunit in LMAN causes stuttering and song sequence changes in adult zebra finches

“…During the critical period for song development, NR2B mRNA levels in LMAN are higher than NR2A 34, 35 . Then as the song becomes crystallized, NR2B expression and currents decreases, and NR2A increases in LMAN 34–36 , causing NMDAR -mediated synaptic currents to shorten (presumably with NR2B or NR2A dimerizing with the ubiquitous NR1 subunit) 37 .…”

“…These developmental changes in LMAN are correlated with developmental changes in the NMDAR (N-methyl-D-aspartate receptor) subunits involved in neural plasticity, NR2A (N-methyl-D-aspartate receptor 2A) and NR2B (N-methyl-D-aspartate receptor 2B) 34, 35 . During the critical period for song development, NR2B mRNA levels in LMAN are higher than NR2A 34, 35 .…”

“…By the time the animals become adults, NR2B mRNA is lower, whereas NR2A mRNA is higher in LMAN compared to the surrounding nidopallium region (adult patterns also seen in the two other vocal learning lineages, parrots and hummingbirds) 38 . Importantly, NDMARs are necessary for normal song development 35, 39 , and LMAN input to RA is regulated primarily by NMDAR 40–42 . These findings are consistent with the hypothesis that the NR2B gene confers increased plasticity to neural circuits 43–45 , and that its downregulation in adult LMAN may contribute to the molecular mechanisms of increased song stereotypy in adults.…”