Genomewide analysis of rat barrel cortex reveals time-and layer-specific mRNA expression changes related to experience-dependent plasticity


Vall├Ęs, A., Boender, A. J., Gijsbers, S., Haast, R. A., Martens, G. J., & de Weerd, P. (2011)

The Journal of Neuroscience, 31(16), 6140-6158.

Abstract

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.

Contribution to the field

This is to our knowledge the first genome-wide assessment of plasticity in barrel cortex induced by an enriched environment (EE) manipulation. Generally impressive were the large numbers of genes that showed significant fold changes (170 up and 31 down at time point 0h; and 28 up and 88 down at time point 4h). The two sets at the two time points were also relatively different (40 overlapping genes). The data thus show a large genomic response involving many transcription factors and late genes regulating a whole spectrum of processes involved in plasticity. In situ hybridization of selected genes furthermore revealed a complex response throughout many brain areas and structures. Interestingly, after a month of exposure to EE, genomewide screening only revealed 29 genes, which showed a pattern of downregulated transcription factors and upregulated neuropeptides associated with interneurons (Valles et al., Learning & Memory, 2015). The latter finding may be compatible with findings of sharpened tuning in sensory areas after perceptual learning (e.g., as reported by Schoups et al., Nature, 2001). Our data base (together with other databases and tools) can be helpful in selecting candidate genes in further research (e.g., fMRI association studies focused on learning-induced plasticity in sensory cortex).

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