Bidirectional regulation of the cAMP response element binding protein encodes spatial map alignment in prism-adapting barn owls.
Bidirectional regulation of the cAMP response element binding protein encodes spatial map alignment in prism-adapting barn owls.
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DOI：
10.1523/jneurosci.1385-08.2008
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发表时间：
2008-10-01
期刊：
影响因子：
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通讯作者：
DeBello WM
中科院分区：
文献类型：
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作者：
Nichols GS;DeBello WM
仓鸮的中脑包含相互对齐的听觉和视觉空间图。在整个生命过程中，地图对齐是通过编码听觉-视觉不匹配程度的指导信号的作用来维持的。由该信号激活的细胞内信号传导途径尚不清楚。在这里，我们测试了 CREB（cAMP 反应元件结合蛋白）提供细胞特异性的指导信息读数的假设。猫头鹰戴着棱镜或控制眼镜，提供丰富的听觉和视觉体验——捕猎活老鼠。使用磷酸化状态特异性 (pCREB) 和 CREB 抗体、共聚焦成像和单个细胞核的免疫荧光测量，在狩猎后 30 分钟内分析 CREB 激活。在对照猫头鹰或适应棱镜的猫头鹰中，经历小的指示信号，下丘外核（ICX）内的细胞核获得的 pCREB/CREB 值的频率分布是单峰的。相比之下，在适应棱镜或重新适应正常条件的猫头鹰中，分布是双峰的：某些细胞接收到正向调节 CREB 的信号，并延伸到 CREB 依赖性基因的转录，而其他细胞则收到负向调节 CREB 的信号。这些变化仅限于接受光学位移输入的下丘子区域，即喙侧 ICX，而在尾侧 ICX 或中央核中并不明显。最后，CREB 调节的地形模式是不连续的，正如从编码离散事件的地形精确信号的作用所预期的那样。这些结果支持一个模型，其中单个细胞内 CREB 激活的程度提供了指导可塑性和学习的指导信号的读数。
The barn owl midbrain contains mutually aligned maps of auditory and visual space. Throughout life, map alignment is maintained through the actions of an instructive signal that encodes the magnitude of auditory-visual mismatch. The intracellular signaling pathways activated by this signal are unknown. Here we tested the hypothesis that CREB (cAMP response element binding protein) provides a cell-specific readout of instructive information. Owls were fitted with prismatic or control spectacles and provided rich auditory-visual experience - hunting live mice. CREB activation was analyzed within 30 minutes of hunting using phosphorylation state-specific (pCREB) and CREB antibodies, confocal imaging and immunofluorescence measurements at individual cell nuclei. In control owls or prism-adapted owls, which experience small instructive signals, the frequency distributions of pCREB/CREB values obtained for cell nuclei within the external nucleus of the inferior colliculus (ICX) were unimodal. In contrast, in owls adapting to prisms or re-adapting to normal conditions, the distributions were bimodal: certain cells had received a signal that positively regulated CREB, and by extension, transcription of CREB-dependent genes, while others a signal that negatively regulated it. These changes were restricted to the sub-region of the inferior colliculus that received optically displaced input, the rostral ICX, and not evident in the caudal ICX or central nucleus. Finally, the topographic pattern of CREB regulation was patchy, not continuous, as expected from the actions of a topographically precise signal encoding discrete events. These results support a model in which the magnitude of CREB activation within individual cells provides a readout of the instructive signal that guides plasticity and learning.