Figure 2: Action potential pattern dependent regulation of gene-regulatory networks.

Neurons were electrically stimulated with two patterns, 18/1 or 90/5 for 2 hr and 5 hr. (A) Hierarchical clustering of log-normalized microarray data showing differential expression of many hundreds of genes in electrically stimulated DRG neurons. (B) Frequency distribution of up- (red) and down-regulated (blue) genes in DRG neurons. Each gene is represented along the x-axis and corresponding log-normalized expression value. Numbers of up- and down-regulated genes are unbalanced, favoring greater transcriptional activation at 5 hr for 18/1 stimulus pattern compared to greater initial activation at the 90/5 stimulus pattern at 2 hr and down-regulation by 5 hr. (C) Venn diagram showing numbers of up- and down-regulated genes at 2 hr and 5 hr for both patterns of electrical activation. Total numbers of regulated genes are given in parenthesis for each time, pattern, and direction of change. In total, 2,501 genes were significantly upregulated by electrical stimulation and 3,424 were significantly down-regulated by electrical stimulation. Of these, a small subset of genes was co-regulated by both patterns. Only 9 activity-regulated genes were co-upregulated independently of pattern or stimulus duration in contrast to 22 genes suppressed by patterned activity. N = 4 replicate experiments per condition.