Motor cortex gene expression during learning of a motor skill

The learning of motor skills requires plastic changes in motor regions of the brain including motor cortex. Motor learning can therefore be regarded as a model system for investigating cortical plasticity. It is known that consolidation of a motor skill requires protein synthesis in motor cortex that happens after the training (Luft et al. J Neurosci 2004, 24:6515). To elucidate which proteins are being synthesized, microarray genechips (Affymetrix, High Wycombe, UK) were used to screen for up- or downregulated genes at three different time points after a 30-min training session (1h, 7h, 24h) of a skilled forelimb reaching movement in rat. Trained rats were compared to rats exposed to identical conditions (handling, cage, feeding) with the exception of forelimb use. ArrayAssist software (Affymetrix) was used to compare the intensities of gene signals on the chip. Multiclass ANOVA with Benjamin-Hochberg (FDR) correction was used to determine significance of gene regulation. Genes were identified using a threshold for probability (p<0.01) and degree of differential expression (1.4 fold).

Overall, the most abundant up-regulation of genes was found at 7h after training (1h: 20, 7h: 77, 24h: 41), whereas most down-regulated genes were found at 24h (1h: 11, 7h: 17, 24h:110). Most up-regulated genes at 7h were signalling proteins. At 24h most down-regulated proteins were signalling proteins as well (Table).

These data demonstrate that the expression of specific genes is modulated in motor cortex during motor learning. Expression peaks around 7h after training and is followed by widespread downregulation below control values. It is likely that up-regulated genes are actually translated into protein, given that protein synthesis is necessary for motor learning. It remains to be determined which of these proteins are necessary mediators of cortical plasticity, in order to gain a deeper understanding of plasticity processes.

Time Point	Regulation	Ion Channel	Metabolic	Nucleic Acid Binding	Signaling	Structural	Transport	Other	Unknown
1h	up		5	2	3	1			9
	down	1	1	1	2	2	1	1	2
7h	up	2	9	4	12	7	1	8	34
	down			1			1	1	6
24h	up	1	2	4	2	2	1	3	26
	down	1	8	2	11	9	2	7	70