Localization of corticotropin-releasing hormone in the human locus coeruleus and pedunculopontine tegmental nucleus: an immunocytochemical and in situ hybridization study.

Abstract

The present study utilized immunocytochemistry and in situ hybridization histochemistry to examine the localization of corticotropin-releasing hormone immunoreactivity and messenger RNA in neurons of the human brainstem. A large population of corticotropin-releasing hormone-immunoreactive neurons appeared in the lateral region of the pontomesencephalic tegmentum. These corticotropin-releasing hormone-containing neurons are predominantly located in the compact subnucleus of the pedunculopontine tegmental nucleus. Proceeding caudally, corticotropin-releasing hormone-immunoreactive neurons in the pedunculopontine tegmental nucleus 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-releasing 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 corticotropin-releasing hormone messenger RNA in the human brainstem is identical to the perikaryal distribution visualized by immunocytochemistry. 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 these neurons on the emulsion autoradiograms. Within the locus coeruleus, the cellular expression of corticotropin-releasing hormone-immunoreactive and corticotropin-releasing hormone messenger RNA is exclusively localized to non-pigmented neurons. The present study confirms a previous finding describing dense corticotropin-releasing hormone-immunoreactive fibers innervating the human locus coeruleus and extends these findings 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-containing neurons in human pontomesencephalic tegmentum form a continuous population of neurons that are positioned anatomically to exert a putative neuromodulatory influence on locus coeruleus neurons.