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

Abstract

Corticotropin-releasing hormone (CRH) receptor type 1 (CRF 1 ) 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 CRF 1 -like immunoreactivity (CRF 1 -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 CRF 1 -immunoreactive (CRF 1 -ir) neurons in the mouse brain, using an antiserum directed against the C-terminus of the receptor. We show that CRF 1 -LI is abundantly yet selectively expressed, and its localization generally overlaps the target regions of CRH-expressing projections and the established distribution of CRF 1 mRNA, with several intriguing exceptions. The most intensely CRF 1 -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 CRF 1 -ir. Finally, intense CRF 1 -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, CRF 1 -LI-labeled neurons are characterized by discrete patterns of the intracellular distribution of the immunoreaction product. While generally membrane associated, CRF 1 -LI may be classified as granular, punctate, or homogenous deposits, consistent with differential membrane localization. The selective distribution and morphological diversity of CRF 1 -ir neurons suggest that CRF 1 may mediate distinct functions in different regions of the mouse brain. Indexing termsCRH; CRF; CRF-R1; rodent; immunocytochemistry; central nervous system Corticotropin-releasing hormone (CRH), a 41-amino acid neuropeptide, is the primary hypothalamic factor involved in controlling the synthesis and release of adrenocorticotropic

Neuronal activity and stress differentially regulate hippocampal and hypothalamic corticotropin-releasing hormone expression in the immature rat

“…In addition, CRH receptors, particularly corticotropinreleasing factor-1, shown to mediate the excitation-promoting actions of CRH, 4 are abundantly expressed in hippocampal pyramidal cells. 2,13,15 These data support the notion that, in the hippocampus, CRH modulates synaptic neurotransmission; in turn, expression of the CRH gene is controlled by hippocampal circuit activation.…”

“…In addition, CRH receptors, particularly corticotropinreleasing factor-1, shown to mediate the excitation-promoting actions of CRH, 4 are abundantly expressed in hippocampal pyramidal cells. 2,13,15 These data support the notion that, in the hippocampus, CRH modulates synaptic neurotransmission; in turn, expression of the CRH gene is controlled by hippocampal circuit activation.The requirement for stimulation of hippocampal neurons 4,14,56 for up-regulation of hippocampal CRH expression, suggested in the current study, is further illustrated by the effects of barbiturates: hyperthermia-induced hippocampal CRH mRNA expression was abolished (in CA1) or attenuated (in CA3) by barbiturate pretreatment, providing clues for the mechanisms for CRH mRNA activation in the hippocampus: Pentobarbital interferes with polysynaptic neurotransmission by modulating GABA A receptors. Indeed, it eliminated the hyperthermia-induced intense hippocampal neuronal stimulation, as evident from behavioral and electrophysiological criteria (Fig.…”

“…15,59 Localization of antibody binding was visualized using diaminobenzidine, as directed in the Vectastain Elite system (Vector, Burlingame, CA).…”

“…24 Abundant target neurons for CRH, expressing cognate receptors, have been demonstrated in the hippocampus. 2,13,15 In addition, physiological effects of CRH on hippocampal neurons have been found, including facilitation of memory retention and increased protein phosphorylation. 10,33 Conversely, abnormalities of CRH-mediated limbic neurotransmission may contribute to neurological disorders such as depression 43 or Alzheimer's disease.…”

Hippocampal neuroplasticity induced by early-life stress: Functional and molecular aspects

“…For example, in CA3, the number of CRH-expressing neurons was approximately 4000 on P18 and declined to approximately 2700 by P60. These CRH-expressing interneurons are primarily basket cells that synapse on somata of hippocampal pyramidal neurons that express the CRH-receptor, CRF 1 [38]. This positions the CRH-expressing neurons to significantly influence pyramidal cell activity and hippocampal information flow.…”