VENs in humans are immunopositive for a host of proteins that may be check details variably related to the role of AIC in the control of autonomic functions (e.g., serotonin receptor 2b [5ht2br]) (Allman et al., 2005), as well as in neuropsychiatric disorders such as schizophrenia (e.g., disrupted-in-schizophrenia-1 [DISC-1]) (Allman et al., 2010), and also craving and addiction (e.g., dopamine D3 receptor [D3]) (Allman et al., 2005). Many macaque VENs are immunopositive for DISC-1 (Figures

2C and 2C′), 5ht2br (Figure 2E), and D3 (Figure 2F). DISC-1 immunopositive VENs are clearly conspicuous, because there are few immunopositive pyramidal neurons (Figure 2C). A stereological estimate as to whether the DISC-1 population in monkeys represents a large fraction of the total number of VENs in the insula, as it does in humans (∼95%) (Allman et al., 2010), would make an

interesting future study. Although all of the proteins examined here are also present in local pyramidal neurons (and are thus not specific markers of the VENs), the similarity in the immunohistochemical characteristics of monkey and human VENs Paclitaxel suggests that subtle, rather than marked, phylogenetic variation may reflect the hypothesized more sophisticated role of the VENs in humans, as suggested in prior examinations of hominoids (Stimpson et al., 2011). Thus, a dedicated stereological analysis of protein expression in the VENs of humans and macaques could help establish the much-needed primate neurochemical model for disorders such as schizophrenia and addiction. Prior comparative studies concluded that concentrations of VENs in primates occur exclusively in humans and great apes (Nimchinsky et al., 1999 and Allman et al., 2010). The present report provides compelling evidence that there is at least a primal anatomical homolog of the human VEN in the monkey AAI (and ACC). There are at least three possible

explanations for this discrepancy Sorafenib with earlier observations. First, the large human VENs unambiguously stand out at low microscope magnifications. Searching for relatively smaller VENs among the densely packed cell population in layer 5 in the monkey required the highest microscope magnification, which would be unusual for anyone accustomed to examining the more obvious VENs in hominids. Second, the cytoskeletal matrix of the small monkey VENs might be more fragile during histological processing than that of the larger human VENs. In the course of this work, we rejected many cases because swelling of the perikarya prevented morphological differentiation. Third, in the major prior study, the number of VENs in humans and great apes was counted in consecutive sections that were apparently spaced at 1 mm intervals (Nimchinsky et al., 1999).