title: Melanin-concentrating hormone neurons release glutamate for feedforward inhibition of the lateral septum.
abstract: Melanin-concentrating hormone (MCH) regulates vital physiological functions, including energy balance and sleep. MCH cells are thought to be GABAergic, releasing GABA to inhibit downstream targets. However, there is little experimental support for this paradigm. To better understand the synaptic mechanisms of mouse MCH neurons, we performed neuroanatomical mapping and characterization followed by optogenetics to test their functional connectivity at downstream targets. Synaptophysin-mediated projection mapping showed that the lateral septal nucleus (LS) contained the densest accumulation of MCH nerve terminals. We then expressed channel rhodopsin-2 in MCH neurons and photostimulated MCH projections to determine their effect on LS activity. Photostimulation of MCH projections evoked a monosynaptic glutamate release in the LS. Interestingly, this led to a feedforward inhibition that depressed LS firing by a robust secondary GABA release. This study presents a circuit analysis between MCH and LS neurons and confirms their functional connection via monosynaptic and polysynaptic pathways. Our findings indicate that MCH neurons are not exclusively GABAergic and reveal a glutamate-mediated, feedforward mechanism that inhibits LS cells.
authors.affiliation: Division of Endocrinology and.
authors.forename: Melissa J S
authors.initials: MJ
authors.lastname: Chee
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115.
authors.forename: Elda
authors.initials: E
authors.lastname: Arrigoni
authors.affiliation: Division of Endocrinology and emaratos@bidmc.harvard.edu.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Maratos-Flier
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D025461:Feedback, Physiological; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D007028:Hypothalamic Hormones / Q000235:genetics / Q000378:metabolism*; D053444:Inhibitory Postsynaptic Potentials; D008543:Melanins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D062308:Optogenetics; D010907:Pituitary Hormones / Q000235:genetics / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000502:physiology; D012686:Septal Nuclei / Q000166:cytology / Q000378:metabolism* / Q000502:physiology
chemical_list: D007028:Hypothalamic Hormones; D008543:Melanins; D010907:Pituitary Hormones; D018698:Glutamic Acid; C019463:melanin-concentrating hormone
keywords: electrophysiology; glutamate; hypothalamus; lateral septum; optogenetics; pathways