title: Mesolimbic neuropeptide W coordinates stress responses under novel environments.
abstract: Neuropeptide B (NPB) and neuropeptide W (NPW) are endogenous neuropeptide ligands for the G protein-coupled receptors NPBWR1 and NPBWR2. Here we report that the majority of NPW neurons in the mesolimbic region possess tyrosine hydroxylase immunoreactivity, indicating that a small subset of dopaminergic neurons coexpress NPW. These NPW-containing neurons densely and exclusively innervate two limbic system nuclei in adult mouse brain: the lateral bed nucleus of the stria terminalis and the lateral part of the central amygdala nucleus (CeAL). In the CeAL of wild-type mice, restraint stress resulted in an inhibition of cellular activity, but this stress-induced inhibition was attenuated in the CeAL neurons of NPW(-/-) mice. Moreover, the response of NPW(-/-) mice to either formalin-induced pain stimuli or a live rat (i.e., a potential predator) was abnormal only when they were placed in a novel environment: The mice failed to show the normal species-specific self-protective and aversive reactions. In contrast, the behavior of NPW(-/-) mice in a habituated environment was indistinguishable from that of wild-type mice. These results indicate that the NPW/NPBWR1 system could play a critical role in the gating of stressful stimuli during exposure to novel environments.
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390; Exploratory Research for Advanced Technology, Yanagisawa Orphan Receptor Project, Japan Science and Technology Agency, Tokyo 135-0064, Japan;
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Motoike
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390; Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224;
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Long
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390; Exploratory Research for Advanced Technology, Yanagisawa Orphan Receptor Project, Japan Science and Technology Agency, Tokyo 135-0064, Japan;
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Arizona Respiratory Center, Department of Medicine, University of Arizona, Tucson, AZ 85724;
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Sinton
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Amber
authors.initials: A
authors.lastname: Skach
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: S Clay
authors.initials: SC
authors.lastname: Williams
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hammer
authors.affiliation: Exploratory Research for Advanced Technology, Yanagisawa Orphan Receptor Project, Japan Science and Technology Agency, Tokyo 135-0064, Japan; Department of Molecular Neuroscience and Integrative Physiology, Faculty of Medicine, Institute of Medical, Pharmacological, and Health Sciences, Kanazawa University, Kanazawa 920-8640, Japan;
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakurai
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390; Exploratory Research for Advanced Technology, Yanagisawa Orphan Receptor Project, Japan Science and Technology Agency, Tokyo 135-0064, Japan; International Institute for Integrative Sleep Medicine, University of Tsukuba, Tsukuba 305-8575, Japan yanagisawa.masa.fu@u.tsukuba.ac.jp.
authors.forename: Masashi
authors.initials: M
authors.lastname: Yanagisawa
mesh_terms: D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal; D066274:Central Amygdaloid Nucleus / Q000378:metabolism* / Q000473:pathology; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D010146:Pain / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D009479:Neuropeptides; C485721:Npbwr1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; C508547:neuropeptide W, mouse; D014446:Tyrosine 3-Monooxygenase
keywords: amygdala; dopaminergic; fear; mouse; pain