1993; Estrada and DeFelipe 1998; Attwell et al. 2010); (2) during an increase

in cortical activity callosal fibers, consistent with their origin from glutamatergic neurons (Barbaresi et al. 1987), release glutamate along their course (Kukley et al. 2007; Ziskin et al. 2007) possibly excitating NO-producing intracallosal neurons (Iadecola and Nedergaard 2007) through NMDA receptors (Garthwaite 1991, 2008); interaction of glutamate with NMDA receptors could therefore be necessary for BOLD responses in the cc as in other CNS regions, where application Inhibitors,research,lifescience,medical of NMDA receptor antagonists attenuates blood flow responses (Iadecola et al. 1996; Nielsen and Lauritzen 2001; Gsell et al. 2006; Hoffmeyer et al. 2007; Busija Inhibitors,research,lifescience,medical et al. 2007; Tiede et al. 2012).

However, a concomitant role of astrocytes in neurovascular coupling (Attwell et al. 2010) in the cc cannot be ruled out. As the present findings indicate that glial cells lack NO-producing enzymes, glutamate released from callosal axons could induce release of vasoactive Inhibitors,research,lifescience,medical agents other than NO from astrocyte end feet, like for example, cyclo-oxygenase (COX) products, whose inhibition significantly reduces vasodilation (Zonta et al. 2003; Takano et al. 2006). Paclitaxel Conclusion In summary, we demonstrated that the adult rat cc contains a sizeable population of NADPH-d+/nNOSIP Inhibitors,research,lifescience,medical neurons amounting to over 2000 intracallosal cells. Their distribution shows a lateromedial gradient, a greater number of neurons being found in the lateral stereotaxic planes than in the more medial ones. NADPH-d+/nNOS+ intracallosal cells present a considerable Inhibitors,research,lifescience,medical morphological heterogeneity. In addition, their location in the ependymal regions of the cc and their association with intracallosal blood vessels suggests an active role for them in regulating both CSF composition and intracallosal blood vessels. Acknowledgments

We are grateful to Silvia Modena for the language review. This paper is dedicated to the memory of Tullio Manzoni (1937–2011) who devoted his life to studying the corpus callosum. Conflict of Interest None declared.
Depression is a complex disorder adversely affecting millions of individuals, with enormous Histamine H2 receptor social and economic costs (WHO 2001). The World Health Organization has predicted depression will be the second leading cause of disability worldwide by 2020 (Murray and Lopez 1996). Despite its public health importance, the biological mechanisms underlying the depression etiology remain uncertain. Studies suggest that genetic factors play an important role in depression (Duffy et al.