Harwell Corey, Burbach Barry, Svoboda Karel, Nedivi Elly
The Picower Center for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 50 Ames Street, E18-670, Cambridge, Massachusetts 02139, USA.
J Neurobiol. 2005 Oct;65(1):85-96. doi: 10.1002/neu.20176.
Regulation of gene transcription by neuronal activity is thought to be key to the translation of sensory experience into long-term changes in synaptic structure and function. Here we show that cpg15, a gene encoding an extracellular signaling molecule that promotes dendritic and axonal growth and synaptic maturation, is regulated in the somatosensory cortex by sensory experience capable of inducing cortical plasticity. Using in situ hybridization, we monitored cpg15 expression in 4-week-old mouse barrel cortex after trimming all whiskers except D1. We found that cpg15 expression is depressed in the deprived barrels and enhanced in the barrel column corresponding to the spared D1 whisker. Changes in cpg15 mRNA levels first appear in layer IV, peak 12 h after deprivation, and then decline rapidly. In layers II/III, changes in cpg15 expression appear later, peak at 24 h, and persist for days. Induction of cpg15 expression is significantly diminished in adolescent as well as adult CREB knockout mice. cpg15's spatio-temporal expression pattern and its regulation by CREB are consistent with a role in experience-dependent plasticity of cortical circuits. Our results suggest that local structural and/or synaptic changes may be a mechanism by which the adult cortex can adapt to peripheral manipulations.
神经元活动对基因转录的调控被认为是将感官体验转化为突触结构和功能长期变化的关键。在此我们表明，cpg15是一个编码促进树突和轴突生长以及突触成熟的细胞外信号分子的基因，在体感皮层中它受能够诱导皮层可塑性的感官体验调控。我们使用原位杂交技术，在修剪掉除D1之外的所有胡须后，监测了4周龄小鼠桶状皮层中cpg15的表达。我们发现，在被剥夺胡须的桶状区域中cpg15表达降低，而在对应留存的D1胡须的桶状柱中表达增强。cpg15 mRNA水平的变化首先出现在IV层，在剥夺后12小时达到峰值，然后迅速下降。在II/III层，cpg15表达的变化出现较晚，在24小时达到峰值，并持续数天。在青少年以及成年CREB基因敲除小鼠中，cpg15表达的诱导显著减少。cpg15的时空表达模式及其受CREB的调控与在皮层回路的经验依赖性可塑性中所起的作用一致。我们的结果表明，局部结构和/或突触变化可能是成年皮层适应外周操作的一种机制。
