title: Sleep architecture and homeostasis in mice with partial ablation of melanin-concentrating hormone neurons.
abstract: Recent reports support a key role of tuberal hypothalamic neurons secreting melanin concentrating-hormone (MCH) in the promotion of Paradoxical Sleep (PS). Controversies remain concerning their concomitant involvement in Slow-Wave Sleep (SWS). We studied the effects of their selective loss achieved by an Ataxin 3-mediated ablation strategy to decipher the contribution of MCH neurons to SWS and/or PS. Polysomnographic recordings were performed on male adult transgenic mice expressing Ataxin-3 transgene within MCH neurons (MCH(Atax)) and their wild-type littermates (MCH(WT)) bred on two genetic backgrounds (FVB/N and C57BL/6). Compared to MCH(WT) mice, MCH(Atax) mice were characterized by a significant drop in MCH mRNAs (-70%), a partial loss of MCH-immunoreactive neurons (-30%) and a marked reduction in brain density of MCH-immunoreactive fibers. Under basal condition, such MCH(Atax) mice exhibited higher PS amounts during the light period and a pronounced SWS fragmentation without any modification of SWS quantities. Moreover, SWS and PS rebounds following 4-h total sleep deprivation were quantitatively similar in MCH(Atax)vs. MCH(WT) mice. Additionally, MCH(Atax) mice were unable to consolidate SWS and increase slow-wave activity (SWA) in response to this homeostatic challenge as observed in MCH(WT) littermates. Here, we show that the partial loss of MCH neurons is sufficient to disturb the fine-tuning of sleep. Our data provided new insights into their contribution to subtle process managing SWS quality and its efficiency rather than SWS quantities, as evidenced by the deleterious impact on two powerful markers of sleep depth, i.e., SWS consolidation/fragmentation and SWA intensity under basal condition and under high sleep pressure.
authors.affiliation: Neuroscience Research Center of Lyon (CRNL), CNRS UMR 5292, INSERM U1028, SLEEP Team, Lyon, France; Université Claude Bernard, Lyon 1, Lyon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Varin
authors.affiliation: Neuroscience Research Center of Lyon (CRNL), CNRS UMR 5292, INSERM U1028, SLEEP Team, Lyon, France; Université Claude Bernard, Lyon 1, Lyon, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Arthaud
authors.affiliation: Neuroscience Research Center of Lyon (CRNL), CNRS UMR 5292, INSERM U1028, SLEEP Team, Lyon, France; Université Claude Bernard, Lyon 1, Lyon, France.
authors.forename: Denise
authors.initials: D
authors.lastname: Salvert
authors.affiliation: Neuroscience Research Center of Lyon (CRNL), CNRS UMR 5292, INSERM U1028, SLEEP Team, Lyon, France; Université Claude Bernard, Lyon 1, Lyon, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Gay
authors.affiliation: Neuroscience Research Center of Lyon (CRNL), CNRS UMR 5292, INSERM U1028, SLEEP Team, Lyon, France; Université Claude Bernard, Lyon 1, Lyon, France.
authors.forename: Paul-Antoine
authors.initials: PA
authors.lastname: Libourel
authors.affiliation: Neuroscience Research Center of Lyon (CRNL), CNRS UMR 5292, INSERM U1028, SLEEP Team, Lyon, France; Université Claude Bernard, Lyon 1, Lyon, France.
authors.forename: Pierre-Hervé
authors.initials: PH
authors.lastname: Luppi
authors.affiliation: Neuroscience Research Center of Lyon (CRNL), CNRS UMR 5292, INSERM U1028, SLEEP Team, Lyon, France; Université Claude Bernard, Lyon 1, Lyon, France.
authors.forename: Lucienne
authors.initials: L
authors.lastname: Léger
authors.affiliation: Neuroscience Research Center of Lyon (CRNL), CNRS UMR 5292, INSERM U1028, SLEEP Team, Lyon, France; Université Claude Bernard, Lyon 1, Lyon, France. Electronic address: patrice.fort@univ-lyon1.fr.
authors.forename: Patrice
authors.initials: P
authors.lastname: Fort
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D002452:Cell Count; D006706:Homeostasis / Q000502:physiology*; D007028:Hypothalamic Hormones / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008543:Melanins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D010907:Pituitary Hormones / Q000378:metabolism*; D017286:Polysomnography; D012890:Sleep / Q000502:physiology*; D013045:Species Specificity
chemical_list: D007028:Hypothalamic Hormones; D008543:Melanins; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone
keywords: Ataxin-3; MCH; REM sleep; Sleep deprivation; Sleep homeostasis; Tuberal hypothalamus