Nichols Grant S, DeBello William M
Department of Neurobiology, Physiology and Behavior, Center for Neuroscience, University of California, Davis, Davis, California 95618, USA.
J Neurosci. 2008 Oct 1;28(40):9898-909. doi: 10.1523/JNEUROSCI.1385-08.2008.
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 min of hunting using phosphorylation state-specific CREB (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 readapting 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, whereas others received a signal that negatively regulated it. These changes were restricted to the subregion of the inferior colliculus that received optically displaced input, the rostral ICX, and were 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.
仓鸮的中脑包含听觉和视觉空间相互对齐的图谱。在其一生中，图谱对齐通过一种编码视听失配程度的指导性信号的作用得以维持。该信号激活的细胞内信号通路尚不清楚。在此，我们测试了一个假说，即CREB（环磷酸腺苷反应元件结合蛋白）提供了指导性信息的细胞特异性读出。给仓鸮佩戴棱镜或对照眼镜，并提供丰富的视听体验：捕食活小鼠。在捕食后30分钟内，使用磷酸化状态特异性CREB（pCREB）和CREB抗体、共聚焦成像以及对单个细胞核的免疫荧光测量来分析CREB的激活情况。在经历小指导性信号的对照仓鸮或适应棱镜的仓鸮中，下丘外侧核（ICX）内细胞核获得的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仓鸮中，分布是双峰的：某些细胞接收到了正向调节CREB以及延伸至CREB依赖性基因转录的信号，而其他细胞接收到的是负向调节它的信号。这些变化局限于下丘接受光学移位输入的子区域，即吻侧ICX，在尾侧ICX或中央核中并不明显。最后，CREB调节的拓扑模式是斑驳的，而非连续的，这与编码离散事件的拓扑精确信号的作用预期一致。这些结果支持了一个模型，即单个细胞内CREB激活的程度提供了指导可塑性和学习的指导性信号的读出。
