Patterned expression of a cocaine- and amphetamine-regulated transcript peptide reveals complex circuit topography in...

The cerebellum (Cb) of mammals and birds consists of an evolutionarily conserved map defined by Purkinje cell (PC) protein expression. In mice, ZebrinII/aldolaseC is expressed in a striking array of stripes in lobules I-V (anterior zone; AZ) and VIII-anterior IX (posterior zone; PZ), whereas the small heat shock protein 25 (HSP25) is expressed in stripes in lobules VI-VII (central zone, CZ) and posterior IX-X (nodular zone, NZ). Little is known about whether molecularly defined afferent subsets terminate within specific PC stripes or whether their topography is conserved across species. Using immunohistochemistry, we demonstrate in adult mice and rats that cocaine- and amphetamine-regulated transcript (CART) expression can be used to partition sensory-motor projections into complex topographic maps. We found that in mice CART was expressed in climbing fiber bands that generally corresponded to the pattern of HSP25-expressing PCs in the CZ/NZ. In contrast, CART was expressed in climbing fiber bands in all four transverse zones of the rat Cb. Within the rat AZ/PZ, climbing fibers terminated selectively within the dendrites of ZebrinII-immunoreactive PCs. In additional experiments, we observed CART expression in loose clusters of spinocerebellar mossy fibers in the mouse AZ/PZ, whereas in rat CART immunoreactive mossy fibers terminated predominantly in the CZ/NZ. We conclude that, although the overall topography of CART-expressing afferents is restricted within a conserved map of PC stripes and transverse zones, their termination patterns also reflect species-specific compartmental features.