In line with its strong GS motifs X score, Ypel5 was behaviorally

In line with its strong GS.motifs.X score, Ypel5 was behaviorally regulated, with lower protein levels observed in area X of birds that sang more motifs ( Figure 8B). Our results for both Reelin and Ypel5 demonstrate expression of multiple members of their respective signaling pathways in area X, with behavioral regulation of each. As further validation, we detected protein signals within area X consistent with expression of Transient Receptor Potential Vanilloid Type 1 (Trpv1), a capsaicin receptor. We selected Trpv1 for validation because of its high MM and selleck screening library GS.motifs.X, and its identification as an ion channel positively

selected for in the songbird lineage (Figure S7B; Warren et al., 2010). TRPV1 is in the dark green Smoothened antagonist and salmon singing-related modules (one probe in each; dark green: MM = 0.85, GS.motifs.X = −0.77; salmon: MM = 0.81, GS.motifs.X = −0.51;

Table S2) and has been linked to endocannabinoid signaling pathways in the mammalian basal ganglia ( Musella et al., 2009 and Maccarrone et al., 2008). Cannabinoid exposure during zebra finch development interferes with song learning ( Soderstrom and Tian, 2004), potentially through synaptic plasticity mechanisms such as modulation of glutamatergic synapses onto medium spiny neurons in area X ( Thompson and Perkel, 2011) and altered area X FoxP2 expression ( Soderstrom and Luo, 2010). In keeping with its strong GS.motifs.X score, we observed lower levels of Trpv1 signal in birds that sang more motifs ( Figure S7B). These findings provide additional biological and literature-based validation of our WGCNA. To our knowledge, this study represents the first identification of basal ganglia gene coexpression networks specialized for vocal behavior, and the first use of

WGCNA to link coexpression modules to a naturally occurring, procedurally learned behavior. We found ∼2,000 genes within the song-specialized striato-pallidal area X, but not in VSP, that were significantly coupled to singing, most of which were members of one of five distinct singing-related modules. MYO10 The three song modules (blue, dark green, orange; Figure 3) were unique to area X, and a given module’s singing-relatedness was highly predictive of its preservation outside of area X, i.e., the more related to singing, the less preserved (Figure 4). The VSP is active during singing, as indicated by IEG expression (Feenders et al., 2008), and we found gene expression levels in VSP and area X to be remarkably similar during singing (Figure 5). Thus, the regional differences we observed in network structure are probably not due to differences in expression levels, and the singing-related modules in area X are probably not a general product of neural activity, but instead reflect area X-specific singing-driven gene regulation patterns.

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