In other words, PCDH17 is expressed along the anatomically Tyrosine Kinase Inhibitor Library connected corticobasal ganglia pathways in a highly topographic manner. Because protocadherin 10 (PCDH10), another δ2-protocadherin family member, is highly expressed in the striatum (Aoki et al., 2003), we next compared expression patterns of both of these proteins in basal ganglia. Double immunostaining of PCDH17 and PCDH10 showed that while PCDH17 is distributed in the anterior striatum, PCDH10 is distributed in the posterior striatum (Figure 2A). Therefore, expression of the two protocadherins
was complementary along the anteroposterior axis. Their distributions are also complementary in the LGP and MGP; PCDH17 displays an inner distribution, but PCDH10 displays an outer distribution within these regions (Figure 2A). Furthermore, in contrast to the distribution of PCDH17 in the posterior SNr, PCDH10 is distributed in the anterior SNr (Figure 2A). Double-fluorescent in situ hybridization demonstrated that both PCDH17 and PCDH10 mRNAs also exhibit complementary
expression patterns in basal ganglia ( Figure S2). Thus, these findings indicate that PCDH17 and PCDH10 delineate topographic features of this pathway. We next compared the protein expression patterns BMS-354825 nmr of PCDH17 and PCDH10 in the cerebral cortex and thalamus, particularly in the prefrontal cortex and the mediodorsal
thalamus, as these regions are anatomically and functionally incorporated into the corticobasal ganglia-thalamocortical loops (McCracken and Grace, 2009; McFarland and Haber, 2002). In the prefrontal cortex, while PCDH17 is distributed in the medial prefrontal cortex, PCDH10 expression is higher in the orbitofrontal cortex, indicating partially complementary expression patterns (Figure 2B). In subregions of the mediodorsal thalamus, PCDH17 and PCDH10 expression are also expressed in a somewhat complementary Astemizole manner (Figure 2C). Thus, expression of PCDH17 and PCDH10 are largely complementary throughout the corticobasal ganglia-thalamocortical loop circuits in a highly topographic manner. We note that expression of PCDH17 and PCDH10 partially overlaps in some cortical and thalamic areas, which could explain the presence of integrative and converging trans-circuits in these areas (Draganski et al., 2008). We examined the subcellular localization of PCDH17 in basal ganglia using high-resolution structured illumination microscopy (SIM) to acquire 3D images with resolution approaching 100 nm (Schermelleh et al., 2008). We performed immunostaining of PCDH17 in addition to VGLUT1 and PSD-95, markers of the pre- and postsynaptic compartments of corticostriatal excitatory synapses, respectively.