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

Abstract

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), and supraoptic nuclei; lower levels of expression are seen in certain cranial nerve and spinal motoneurons and in small populations of neurons in the forebrain. Additional sites of UCN mRNA and peptide expression detected only in colchicine-treated rats are considered to be minor ones. UCN-immunoreactive projections in brain are predominantly descending and largely consistent with central projections attributed to the EW and LSO, targeting principally accessory optic, precerebellar, and auditory structures, as well as the spinal intermediate gray. Although neither the EW nor LSO are known to project to the forebrain, UCN-ir neurons in the EW were identified that project to the lateral septal nucleus, which houses a prominent UCN-ir terminal field. Although substantial UCN-ir projections were observed to several brainstem cell groups that express CRF-R2, including the dorsal raphe and interpeduncular nuclei and the nucleus of the solitary tract (NTS), most prominent 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 mechanisms would appear to derive principally by virtue of projections to the spinal intermediolateral column, the NTS, and the paraventricular nucleus. Several observations, including the lack of a pervasive relationship of UCN-ir projections with CRF-R2-expressing targets, support the existence of still additional CRF-related peptides in mammalian brain.