LOCALIZATION OF CORTICOTROPIN-RELEASING HORMONE IN THE HUMAN LOCUS-COERULEUS AND PEDUNCULOPONTINE TEGMENTAL NUCLEUS - AN IMMUNOCYTOCHEMICALAND IN-SITU HYBRIDIZATION STUDY

The present study utilized immunocytochemistry and in situ hybridizati on histochemistry to examine the localization of corticotropin-releasi ng hormone immunoreactivity and messenger RNA in neurons of the human brainstem. A large population of corticotropin-releasing hormone-immun oreactive neurons appeared in the lateral region of the pontomesenceph alic tegmentum. These corticotropin-releasing hormone-containing neuro ns are predominantly located in the compact subnucleus of the peduncul opontine tegmental nucleus. Proceeding caudally, corticotropin-releasi ng hormone-immunoreactive neurons in the pedunculopontine tegmental nu cleus travel in a dorsomedial direction approaching the ventral border of the locus coeruleus in a dispersed fashion and cluster in a region ventromedial to the locus coeruleus which corresponds to the ventral aspect of the laterodorsal tegmental nucleus. Dense corticotropin-rele asing hormone-immunoreactive fibers are present in the dorsal portion of the locus coeruleus and are most prominent in the middle to rostral levels of the nucleus. The cellular and regional localization of cort icotropin-releasing hormone messenger RNA in the human brainstem is id entical to the perikaryal distribution visualized by immunocytochemist ry. Neurons in the laterodorsal tegmental nucleus and pedunculopontine tegmental nucleus express abundant levels of corticotropin-releasing hormone messenger RNA as revealed by dense silver grains overlying the se neurons on the emulsion autoradiograms. Within the locus coeruleus, the cellular expression of corticotropin-releasing hormone-immunoreac tive and corticotropin-releasing hormone messenger RNA is exclusively localized to non-pigmented neurons. The present study confirms a previ ous finding describing dense corticotropin-releasing hormone-immunorea ctive fibers innervating the human locus coeruleus and extends these f indings by identifying corticotropin-releasing hormone immunoreactive and corticotropin-releasing hormone messenger RNA-containing perikarya in the pedunculopontine tegmental nucleus, in the ventral portion of the laterodorsal tegmental nucleus and in the locus coeruleus proper. From morphological observations, the corticotropin-releasing hormone-c ontaining neurons in human pontomesencephalic tegmentum form a continu ous population of neurons that are positioned anatomically to exert a putative neuromodulatory influence on locus coeruleus neurons.