Immunocytochemical Distribution of Corticotropin-Releasing Hormone Receptor Type-1 (CRF1)-Like Immunoreactivity in the Mouse Brain: Light Microscopy Analysis Using an Antibody Directed Against the C-Terminus

摘要

Corticotropin-releasing hormone (CRH) receptor type 1 (CRF1) is a member of the receptor family mediating the effects of CRH, a critical neuromediator of stress-related endocrine, autonomic, and behavioral responses. The detailed organization and fine localization of CRF1-like immunoreactivity (CRF1-LI) containing neurons in the rodent have not been described, and is important to better define the functions of this receptor. Here we characterize in detail the neuroanatomical distribution of CRF1-immunoreactive (CRF1-ir) neurons in the mouse brain, using an antiserum directed against the C-terminus of the receptor. We show that CRF1-LI is abundantly yet selectively expressed, and its localization generally overlaps the target regions of CRH-expressing projections and the established distribution of CRF1 mRNA, with several intriguing exceptions. The most intensely CRF1-LI-labeled neurons are found in discrete neuronal systems, i.e., hypothalamic nuclei (paraventricular, supraoptic, and arcuate), major cholinergic and monoaminergic cell groups, and specific sensory relay and association thalamic nuclei. Pyramidal neurons in neocortex and magnocellular cells in basal amygdaloid nucleus are also intensely CRF1-ir. Finally, intense CRF1-LI is evident in brainstem auditory associated nuclei and several cranial nerves nuclei, as well as in cerebellar Purkinje cells. In addition to their regional specificity, CRF1-LI-labeled neurons are characterized by discrete patterns of the intracellular distribution of the immunoreaction product. While generally membrane associated, CRF1-LI may be classified as granular, punctate, or homogenous deposits, consistent with differential membrane localization. The selective distribution and morphological diversity of CRF1-ir neurons suggest that CRF1 may mediate distinct functions in different regions of the mouse brain.