Cheng Hui-Yun, Clayton David F
Department of Cell and Structural Biology and Beckman Institute, University of Illinois, Urbana, Illinois 61801, USA.
J Neurosci. 2004 Aug 25;24(34):7503-13. doi: 10.1523/JNEUROSCI.1405-04.2004.
The sound of tape-recorded birdsong triggers a set of behavioral and physiological responses in zebra finches, including transcriptional activation of the zenk gene in the auditory forebrain. Song repetition leads to the stimulus-specific habituation of these responses. To gain insight into the mechanisms that couple auditory experience to gene regulation, we monitored the phosphorylation of the zebra finch extracellular signal-regulated kinase (ERK) protein by immunoblotting. Initial presentations of novel song (but not tones or noise) resulted in a rapid increase in ERK phosphorylation, followed by a return to basal levels within 5 min. This response was localized to the auditory forebrain where the zenk gene is activated. Sustained repetition of one song caused a selective habituation of the ERK response: a different song triggered another cycle of ERK phosphorylation without altering the habituated response to the first. To test directly for a role of ERK in experience-dependent zenk gene regulation, we infused an inhibitor of mitogen-activated and extracellular-regulated protein kinase kinase (MEK-1; the enzyme responsible for ERK activation) unilaterally into one auditory lobule just before song stimulation. The song-induced increase in zenk mRNA was blocked on the side of the injection, but not on the contralateral (uninfused) side. These results show that ERK phosphorylation is necessary for the initiation of the zenk gene response to novel song and identify ERK as a plausible site of signal integration underlying the selective habituation of genomic responses to a repeated song.
录制的鸟鸣声会触发斑胸草雀一系列行为和生理反应，包括听觉前脑区zenk基因的转录激活。歌曲重复会导致这些反应出现刺激特异性习惯化。为深入了解将听觉体验与基因调控联系起来的机制，我们通过免疫印迹法监测了斑胸草雀细胞外信号调节激酶（ERK）蛋白的磷酸化情况。新歌曲（而非音调或噪音）的初次呈现会导致ERK磷酸化迅速增加，随后在5分钟内恢复到基础水平。这种反应定位于激活zenk基因的听觉前脑区。一首歌曲的持续重复会导致ERK反应出现选择性习惯化：不同的歌曲会触发另一个ERK磷酸化循环，而不会改变对第一首歌曲的习惯化反应。为直接测试ERK在经验依赖性zenk基因调控中的作用，我们在歌曲刺激前，向一侧听觉小叶单侧注入丝裂原活化及细胞外调节蛋白激酶激酶（MEK-1；负责ERK激活的酶）的抑制剂。注射侧歌曲诱导的zenk mRNA增加被阻断，但对侧（未注入）未受影响。这些结果表明，ERK磷酸化是zenk基因对新歌曲反应启动所必需的，并确定ERK是基因组对重复歌曲选择性习惯化潜在信号整合的一个合理位点。
