The orexin/hypocretin (ORX) system is involved in physiological processes such as feeding, energy metabolism, and the control of sleep and wakefulness. The ORX system may drive the aminergic and cholinergic activities that control sleep and wakefulness states because of the ORX fiber projections to the aminergic and cholinergic cell clusters. The biological mechanisms and relevance of the interactions between these neurotransmitter systems are poorly understood. We studied these systems in zebrafish, a model organism in which it is possible to simultaneously study these systems and their interactions.We cloned a zebrafish prepro-ORX gene that encodes for the two functional neuropeptides orexin-A (ORX-A) and orexin-B (ORX-B). The prepro-ORX gene of the zebrafish consisted of one exon in contrast to mammals. The sequence of the ORX-A peptide of the zebrafish was less conserved than the ORX-B peptide compared with other vertebrates. By using in situ hybridization and immunohistochemistry, we found that the organization of the ORX system of zebrafish was similar to the ORX system in mammals, including a hypothalamic cell cluster and widespread fiber projections. The ORX system of the zebrafish showed a unique characteristic with an additional putatively ORX-containing cell group. The ORX system innervated several aminergic nuclei, raphe, locus ceruleus, the mesopontine-like area, dopaminergic clusters, and histaminergic neurons. A reciprocal relationship was found between the ORX system and several aminergic systems. Our results suggest that the architecture of these neurotransmitter systems is conserved in vertebrates and that these neurotransmitter systems in zebrafish may be involved in regulation of states of wakefulness and energy homeostasis by similar mechanisms as those in mammals.

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Alternative splicing has an important role in the tissue-specific regulation of gene expression. Here we report that similar to the human NPFF2 receptor, the mouse NPFF2 receptor is alternatively spliced. In human the presence of three alternatively spliced receptor variants were verified, whereas two NPFF2 receptor variants were identified in mouse. The alternative splicing affected the 5 0 untranslated region of the mouse receptor and the variants in mouse were differently distributed. The mouse NPFF system may also have species-specific features since the NPFF2 receptor mRNA expression differs from that reported for rat.

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A large family of G-protein-coupled receptors, with sequence homology to the oncoprotein MAS1, has been shown to be specifically expressed in nociceptive sensory neurons. Significance and context Vertebrate peripheral chemosensory neurons express large families of G-protein-coupled receptors (GPCRs), reflecting the diversity of ligands that these sensory systems detect. In contrast, peripheral somatosensory neurons within the body are thought not to discriminate specifically between different chemical ligands, but rather to respond to polymodal stimuli using broadly tuned receptors such as the vanilloid receptor I (VRI). Dorsal root ganglia (DRGs) contain diverse subpopulations of primary sensory neurons. One category comprises the nociceptors, which respond to a variety of noxious thermal, mechanical and chemical stimuli that cause acute pain. These receptors also mediate the chronic pain associated with inflammatory responses or nerve injury (neuropathic pain). Dong et al. describe a gene family consisting of nearly 50 MAS1-related GPCR genes-Mas-related genes (mrgs)whose expression indicates an unanticipated degree of molecular diversity among DRG sensory neurons.