Urocortin expression in rat brain: Evidence against a pervasive relationship of urocortin-containing projections with targets bearing type 2 CRF receptors

Histochemical and axonal transport methods were used to clarify the central organization of cells and fibers that express urocortin (UCN), a recently discovered corticotropin-releasing factor (CRF)-related neuropeptide, which has been proposed as an endogenous ligand for type 2 CRF receptors (CRF-R2 ). Neurons that display both UCN mRNA and peptide expression were found to be centered in the Edinger-Westphal (EW), lateral superior olivary (LSO), a nd supraoptic nuclei; lower levels of expression are seen in certain crania l nerve and spinal motoneurons and in small populations of neurons in the f orebrain. Additional sites of UCN mRNA and peptide expression detected only in colchicine-treated rats are considered to be minor ones. UCN-immunoreac tive projections in brain are predominantly descending and largely consiste nt with central projections attributed to the EW and LSO, targeting princip ally accessory optic, precerebellar, and auditory structures, as well as th e spinal intermediate gray. Although neither the EW nor LSO are known to pr oject to the forebrain, UCN-ir neurons in the EW were identified that proje ct to the lateral septal nucleus, which houses a prominent UCN-ir terminal field. Although substantial UCN-ir projections were observed to several bra instem cell groups that express CRF-R2, including the dorsal raphe and inte rpeduncular nuclei and the nucleus of the solitary tract (NTS), most promin ent seats of CRF-R2 expression were found to contain inputs immunopositive for piscine urotensin I, but not rat UCN. The results define a central UCN system whose organization suggests a principal involvement in motor control and sensorimotor integration; its participation in stress-related mechanis ms would appear to derive principally by virtue of projections to the spina l intermediolateral column, the NTS, and the paraventricular nucleus. Sever al observations, including the lack of a pervasive relationship of UCN-ir p rojections with CRF-R2-expressing targets, support the existence of still a dditional CRF-related peptides in mammalian brain. (C) 1999 Wiley-Liss, Inc .