title: The hypothalamic NPVF circuit modulates ventral raphe activity during nociception.
abstract: RFamide neuropeptide VF (NPVF) is expressed by neurons in the hypothalamus and has been implicated in nociception, but the circuit mechanisms remain unexplored. Here, we studied the structural and functional connections from NPVF neurons to downstream targets in the context of nociception, using novel transgenic lines, optogenetics, and calcium imaging in behaving larval zebrafish. We found a specific projection from NPVF neurons to serotonergic neurons in the ventral raphe nucleus (vRN). We showed NPVF neurons and vRN are suppressed and excited by noxious stimuli, respectively. We combined optogenetics with calcium imaging and pharmacology to demonstrate that stimulation of NPVF cells suppresses neuronal activity in vRN. During noxious stimuli, serotonergic neurons activation was due to a suppression of an inhibitory NPVF-ventral raphe peptidergic projection. This study reveals a novel NPVF-vRN functional circuit modulated by noxious stimuli in vertebrates.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: Romain
authors.initials: R
authors.lastname: Madelaine
authors.affiliation: Department of Bioengineering and CNC program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Lovett-Barron
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Halluin
authors.affiliation: Department of Bioengineering and CNC program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Andalman
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: Gemini M
authors.initials: GM
authors.lastname: Skariah
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: Louis C
authors.initials: LC
authors.lastname: Leung
authors.affiliation: Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Burns
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.|INSERM U1024, Ecole Normale Supérieure Paris, 75005, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Mourrain
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D007031:Hypothalamus / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism*; D059225:Nociception; D011903:Raphe Nuclei / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D015027:Zebrafish / Q000378:metabolism*
chemical_list: D009479:Neuropeptides; C503959:neuropeptide VF; D012701:Serotonin