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

Male zebra finches are most apt to mimic songs heard between posthatch days (PHD) 35 and 65, and this vocal learning depends, in part, on the activation of N-methyl-D-aspartate receptors (NMDAR) within a discrete forebrain circuit that includes the lateral magnocellular nucleus of the anterior neostriatum (lMAN) and area X. Using in situ hybridization, we show that transcripts for both the constitutive NMDAR subunit NR1 and the modulatory subunit NR2B decrease abruptly in the lMAN between PHD20 and 40. This downregulation corresponds to the onset of song learning and a transition from slow to faster NMDAR currents in lMAN neurons. In area X, NR1 mRNA increases as NR2B mRNA decreases during song development. To understand how these changes in NMDAR mRNA might regulate song learning, we next investigated how manipulations that influence song development affect NMDAR mRNA expression. Early isolation from conspecific song (which delays closure of the sensitive period for song learning) selectively increases NR2B, but not NR1 mRNA, within lMAN at PHD60. In contrast, exposure to testosterone beginning at PHD20 (which impairs song development and hastens the developmental transition to faster NMDAR current kinetics within lMAN) accelerates the decline in NR2B mRNA in lMAN, again without affecting NR1 transcript levels. Neither manipulation significantly effects NR1 or NR2B mRNA levels in area X. Our data suggest that developmental changes in the expression of specific NMDAR subunits may regulate periods of neural and behavioral plasticity and that flexibility in the timing of these sensitive periods may be achieved through experience and/or hormone-dependent modulation of NMDAR gene expression.