Department of Neurocognition, Faculty of Psychology and Neurosciences, Maastricht University, 6200 MD Maastricht, The Netherlands.
J Neurosci. 2011 Apr 20;31(16):6140-58. doi: 10.1523/JNEUROSCI.6514-10.2011.
Because of its anatomical organization, the rodent whisker-to-barrel system is an ideal model to study experience-dependent plasticity. Manipulation of sensory input causes changes in the properties of the barrels at the physiological, structural, and functional levels. However, much less is known about the molecular events underlying these changes. To explore such molecular events, we have used a genomewide approach to identify key genes and molecular pathways involved in experience-induced plasticity in the barrel cortex of adult rats. Given the natural tendency of rats to explore novel objects, exposure to an enriched environment (EE) was used to stimulate the activity of the whisker-to-barrel cortex in vivo. Microarray analysis at two different time points after EE revealed differential expression of genes encoding transcription factors, including nuclear receptors, as well as of genes involved in the regulation of synaptic plasticity, cell differentiation, metabolism, and, surprisingly, blood vessel morphogenesis. These expression differences reflect changes in somatosensory information processing because unilateral whisker clipping showed EE-induced differential expression patterns in the spared versus deprived barrel cortex. Finally, in situ hybridization revealed cortical layer patterns specific for each selected gene. Together, the present study offers the first genomewide exploration of the key genes regulated by somatosensory stimulation in the barrel cortex and thus provides a solid experimental framework for future in-depth analysis of the mechanisms underlying experience-dependent plasticity.
由于其解剖组织,啮齿动物的胡须-桶状系统是研究经验依赖性可塑性的理想模型。对感觉输入的操纵会导致在生理、结构和功能水平上的桶状结构的特性发生变化。然而,关于这些变化背后的分子事件知之甚少。为了探索这些分子事件,我们使用全基因组方法来鉴定参与成年大鼠桶状皮层中经验诱导可塑性的关键基因和分子途径。鉴于大鼠探索新物体的自然倾向,将丰富环境(EE)暴露用于在体内刺激胡须-桶状皮层的活动。在 EE 后两个不同时间点的微阵列分析显示,包括核受体在内的转录因子编码基因以及参与突触可塑性、细胞分化、代谢调节的基因的表达存在差异,令人惊讶的是,还包括血管形态发生的基因。这些表达差异反映了躯体感觉信息处理的变化,因为单侧胡须修剪显示出在受刺激和未受刺激的桶状皮层之间 EE 诱导的差异表达模式。最后,原位杂交揭示了每个选定基因的皮质层模式。总之,本研究首次对感觉刺激调节的桶状皮层中的关键基因进行了全基因组探索,从而为未来对经验依赖性可塑性的机制进行深入分析提供了坚实的实验框架。