title: Genetic deletion of melanin-concentrating hormone neurons impairs hippocampal short-term synaptic plasticity and hippocampal-dependent forms of short-term memory.
abstract: The cognitive role of melanin-concentrating hormone (MCH) neurons, a neuronal population located in the mammalian postero-lateral hypothalamus sending projections to all cortical areas, remains poorly understood. Mainly activated during paradoxical sleep (PS), MCH neurons have been implicated in sleep regulation. The genetic deletion of the only known MCH receptor in rodent leads to an impairment of hippocampal dependent forms of memory and to an alteration of hippocampal long-term synaptic plasticity. By using MCH/ataxin3 mice, a genetic model characterized by a selective deletion of MCH neurons in the adult, we investigated the role of MCH neurons in hippocampal synaptic plasticity and hippocampal-dependent forms of memory. MCH/ataxin3 mice exhibited a deficit in the early part of both long-term potentiation and depression in the CA1 area of the hippocampus. Post-tetanic potentiation (PTP) was diminished while synaptic depression induced by repetitive stimulation was enhanced suggesting an alteration of pre-synaptic forms of short-term plasticity in these mice. Behaviorally, MCH/ataxin3 mice spent more time and showed a higher level of hesitation as compared to their controls in performing a short-term memory T-maze task, displayed retardation in acquiring a reference memory task in a Morris water maze, and showed a habituation deficit in an open field task. Deletion of MCH neurons could thus alter spatial short-term memory by impairing short-term plasticity in the hippocampus. Altogether, these findings could provide a cellular mechanism by which PS may facilitate memory encoding. Via MCH neuron activation, PS could prepare the day's learning by increasing and modulating short-term synaptic plasticity in the hippocampus.
authors: Centre National De La Recherche Scientifique (CNRS), Unité Mixte De Recherche 5292, Institut National De La Santé Et De La Recherche Médicale (INSERM), Unité 1028, Lyon, France.|Forgetting and Cortical Dynamics, Lyon Neuroscience Research Center, F-69008, Lyon, France.|Lyon Neuroscience Research Center, CRNL, University Lyon 1, F-69000, Lyon, France.
authors: Léa
authors: L
authors: Le Barillier
authors: Centre National De La Recherche Scientifique (CNRS), Unité Mixte De Recherche 5292, Institut National De La Santé Et De La Recherche Médicale (INSERM), Unité 1028, Lyon, France.|Lyon Neuroscience Research Center, CRNL, University Lyon 1, F-69000, Lyon, France.|Physiopathology of the Sleep Neuronal Networks, Lyon Neuroscience Research Center, F-69008, Lyon, France.
authors: Lucienne
authors: L
authors: Léger
authors: Centre National De La Recherche Scientifique (CNRS), Unité Mixte De Recherche 5292, Institut National De La Santé Et De La Recherche Médicale (INSERM), Unité 1028, Lyon, France.|Lyon Neuroscience Research Center, CRNL, University Lyon 1, F-69000, Lyon, France.|Physiopathology of the Sleep Neuronal Networks, Lyon Neuroscience Research Center, F-69008, Lyon, France.
authors: Pierre-Hervé
authors: PH
authors: Luppi
authors: Centre National De La Recherche Scientifique (CNRS), Unité Mixte De Recherche 5292, Institut National De La Santé Et De La Recherche Médicale (INSERM), Unité 1028, Lyon, France.|Lyon Neuroscience Research Center, CRNL, University Lyon 1, F-69000, Lyon, France.|Physiopathology of the Sleep Neuronal Networks, Lyon Neuroscience Research Center, F-69008, Lyon, France.
authors: Patrice
authors: P
authors: Fort
authors: Centre National De La Recherche Scientifique (CNRS), Unité Mixte De Recherche 5292, Institut National De La Santé Et De La Recherche Médicale (INSERM), Unité 1028, Lyon, France.|Forgetting and Cortical Dynamics, Lyon Neuroscience Research Center, F-69008, Lyon, France.|Lyon Neuroscience Research Center, CRNL, University Lyon 1, F-69000, Lyon, France.
authors: Gaël
authors: G
authors: Malleret
authors: Centre National De La Recherche Scientifique (CNRS), Unité Mixte De Recherche 5292, Institut National De La Santé Et De La Recherche Médicale (INSERM), Unité 1028, Lyon, France.|Forgetting and Cortical Dynamics, Lyon Neuroscience Research Center, F-69008, Lyon, France.|Lyon Neuroscience Research Center, CRNL, University Lyon 1, F-69000, Lyon, France.
authors: Paul-Antoine
authors: PA
authors: Salin
mesh_terms: D000818:Animals; D000067699:Ataxin-3 / Q000235:genetics; D001522:Behavior, Animal / Q000502:physiology*; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D007028:Hypothalamic Hormones / Q000235:genetics / Q000502:physiology*; D007031:Hypothalamus / Q000166:cytology* / Q000378:metabolism; D008543:Melanins / Q000235:genetics / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010907:Pituitary Hormones / Q000235:genetics / Q000502:physiology*; D012895:Sleep, REM / Q000502:physiology*
chemical_list: D007028:Hypothalamic Hormones; D008543:Melanins; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone; D000067699:Ataxin-3; C511594:Atxn3 protein, mouse
keywords: Morris water maze; T-maze task; long-term potentiation (LTP); paradoxical sleep (rapid eye movement, REM; post-tetanic potentiation (PTP); sleep)