title: Hypothalamic leptin-neurotensin-hypocretin neuronal networks in zebrafish.
abstract: Neurotensin (NTS) is a 13 amino acid neuropeptide that is expressed in the hypothalamus. In mammals, NTS-producing neurons that express leptin receptor (LepRb) regulate the function of hypocretin/orexin (HCRT) and dopamine neurons. Thus, the hypothalamic leptin-NTS-HCRT neuronal network orchestrates key homeostatic output, including sleep, feeding, and reward. However, the intricate mechanisms of the circuitry and the unique role of NTS-expressing neurons remain unclear. We studied the NTS neuronal networks in zebrafish and cloned the genes encoding the NTS neuropeptide and receptor (NTSR). Similar to mammals, the ligand is expressed primarily in the hypothalamus, while the receptor is expressed widely throughout the brain in zebrafish. A portion of hypothalamic nts-expressing neurons are inhibitory and some coexpress leptin receptor (lepR1). As in mammals, NTS and HCRT neurons are localized adjacently in the hypothalamus. To track the development and axonal projection of NTS neurons, the NTS promoter was isolated. Transgenesis and double labeling of NTS and HCRT neurons showed that NTS axons project toward HCRT neurons, some of which express ntsr. Moreover, another target of NTS neurons is ntsr-expressing dopaminergeric neurons. These findings suggest structural circuitry between leptin, NTS, and hypocretinergic or dopaminergic neurons and establish the zebrafish as a model to study the role of these neuronal circuits in the regulation of feeding, sleep, and reward.
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel; The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
authors.forename: Talia
authors.initials: T
authors.lastname: Levitas-Djerbi
authors.forename: Laura
authors.initials: L
authors.lastname: Yelin-Bekerman
authors.forename: Tali
authors.initials: T
authors.lastname: Lerer-Goldshtein
authors.forename: Lior
authors.initials: L
authors.lastname: Appelbaum
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004298:Dopamine / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007031:Hypothalamus / Q000033:anatomy & histology* / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D009434:Neural Pathways / Q000033:anatomy & histology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism*; D000068797:Orexins; D054411:Receptors, Leptin / Q000378:metabolism; D018028:Receptors, Neurotensin / Q000378:metabolism; D015027:Zebrafish / Q000033:anatomy & histology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin; D009479:Neuropeptides; D000068797:Orexins; D054411:Receptors, Leptin; D018028:Receptors, Neurotensin; D029961:Zebrafish Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D009496:Neurotensin; D004298:Dopamine
keywords: Danio rerio; RRID; hypothalamus; leptin receptor; neurotensin receptor; orexin