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仓鸮听觉定位通路中与指导性学习相关的转录组变化。

Transcriptome changes associated with instructed learning in the barn owl auditory localization pathway.

作者信息

Swofford Janet A, DeBello William M

机构信息

Department of Neurobiology, Physiology, and Behavior, Center for Neuroscience, University of California-Davis, Davis, CA 95616, USA.

出版信息

Dev Neurobiol. 2007 Sep 15;67(11):1457-77. doi: 10.1002/dneu.20458.

DOI:10.1002/dneu.20458
PMID:17526003
Abstract

Owls reared wearing prismatic spectacles learn to make adaptive orienting movements. This instructed learning depends on re-calibration of the midbrain auditory space map, which in turn involves the formation of new synapses. Here we investigated whether these processes are associated with differential gene expression, using longSAGE. Newly fledged owls were reared for 8-36 days with prism or control lenses at which time the extent of learning was quantified by electrophysiological mapping. Transciptome profiles were obtained from the inferior colliculus (IC), the major site of synaptic plasticity, and the optic tectum (OT), which provides an instructive signal that controls the direction and extent of plasticity. Twenty-two differentially expressed sequence tags were identified in IC and 36 in OT, out of more than 35,000 unique tags. Of these, only four were regulated in both structures. These results indicate that regulation of two largely independent gene clusters is associated with synaptic remodeling (in IC) and generation of the instructive signal (in OT). Real-time PCR data confirmed the changes for two transcripts, ubiquitin/polyubiquitin and tyrosine 3-monooxgenase/tryotophan 5-monooxygenase activation protein, theta subunit (YWHAQ; also referred to as 14-3-3 protein). Ubiquitin was downregulated in IC, consistent with a model in which protein degradation pathways act as an inhibitory constraint on synaptogenesis. YWHAQ was up-regulated in OT, indicating a role in the synthesis or delivery of instructive information. In total, our results provide a path towards unraveling molecular cascades that link naturalistic experience with synaptic remodeling and, ultimately, with the expression of learned behavior.

摘要

戴着棱镜眼镜饲养的猫头鹰学会了做出适应性定向运动。这种指导性学习依赖于中脑听觉空间图谱的重新校准,而这反过来又涉及新突触的形成。在这里,我们使用长链分析基因表达标签(longSAGE)研究了这些过程是否与基因表达差异有关。刚出巢的猫头鹰分别佩戴棱镜或对照镜片饲养8至36天,此时通过电生理图谱对学习程度进行量化。从突触可塑性的主要部位下丘(IC)和提供控制可塑性方向和程度的指导性信号的视顶盖(OT)获取转录组图谱。在超过35000个独特标签中,在IC中鉴定出22个差异表达的序列标签,在OT中鉴定出36个。其中,只有4个在两个结构中都受到调控。这些结果表明,两个基本独立的基因簇的调控与突触重塑(在IC中)和指导性信号的产生(在OT中)有关。实时聚合酶链反应(PCR)数据证实了泛素/多聚泛素和酪氨酸3-单加氧酶/色氨酸5-单加氧酶激活蛋白θ亚基(YWHAQ;也称为14-3-3蛋白)这两个转录本的变化。泛素在IC中下调,这与蛋白质降解途径对突触发生起抑制性约束作用的模型一致。YWHAQ在OT中上调,表明其在指导性信息的合成或传递中起作用。总的来说,我们的结果为揭示将自然体验与突触重塑以及最终与习得行为表达联系起来的分子级联反应提供了一条途径。

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Hippocampal dysregulation of synaptic plasticity-associated proteins with age-related cognitive decline.随着年龄相关认知能力下降,海马体中与突触可塑性相关蛋白的调节紊乱。
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