0 × 10−4; SERPINF1, PRDM8, NEUROD2, RTN4R, CA10, and MEF2C). The hub genes of the Hs_brown module are significantly enriched for genes involved in regulation of G protein-coupled receptor protein signaling (p = 3.0 × 10−7; RGS9, RGS14, RGS20, and GNG7). The most highly connected gene in the Hs_brown module FK228 mw is PPP1R1B, or DARPP-32, which is a critical mediator of dopamine signaling in medium spiny neurons

in the striatum ( Walaas and Greengard, 1984). In addition, five other hubs in the Hs_brown module (ADORA2A, GNG7, PDE10A, PRKCH, and RXRG) overlap with the top 25 cell-type-specific proteins in Drd1 or Drd2 striatal neurons in mouse characterized by translational profiling ( Doyle et al., 2008). The hub gene ADORA2A also overlaps with the top differentially expressed genes from microarray profiling of striatal neurons in mouse ( Lobo et al., 2006). When considering all of the genes in the conserved CN modules, Navitoclax mouse we also find a high level of confirmation: six genes overlap with striatal microarrays (ADORA2A,

CALB1, HBEGF, NRXN1, STMN2, and SYT6), eight genes overlap with Drd1 translational profiling (ADORA2A, BCL11B, GNG7, GPR6, GPR88, MN1, PDE10A, and RXRG), and nine genes overlap with Drd2 translational profiling (ADRA2C, ERC2, EYA1, KCNIP2, MYO5B, PDE10A, PDYN, PRKCH, and WNT2). Interestingly, four CN hub genes have been implicated in addiction, three are involved in alcohol addiction (MEF2C, RGS9, and VSNL1), one is involved

in nicotine addiction (GABBR2) ( Li et al., 2008), and two CN hub genes have been linked to obsessive-compulsive disorder (HTR1D and HTR2C) ( Grados, 2010). Taken together, this cross-species no conservation and link to disease has implications for pharmacotherapeutics of neuropsychiatric diseases being developed in rodent models because these data showing conservation between primates and mice further validate rodents as appropriate models for striatal function in humans. GO analysis of FP hub genes reveals an enrichment of genes involved in neural tube development (FZD3, PAX7, PSEN2, and SMO), and regulation of synaptic plasticity (ARC, KRAS, and STAR). However, the majority of FP and HP hub genes are not enriched for specific ontological categories. These results emphasize the importance of these human-specific modules as it suggests that due to their unique expression patterns in the human brain, very little is known about the coordinated function of these genes. Finally, at least one of the conserved modules that was not associated with a particular brain region, Hs_cyan, does overlap with a previously identified module containing an enrichment of genes involved in ATP synthesis and the mitochondrion ( Oldham et al., 2008). These data suggest that genes important for subcellular components important in all brain regions throughout evolution may drive some of the network eigengenes.