title: Dichotomous cellular properties of mouse orexin/hypocretin neurons.
abstract: Hypothalamic hypocretin/orexin (Hcrt/Orx) neurons recently emerged as critical regulators of sleep–wake cycles, reward seeking and body energy balance. However, at the level of cellular and network properties, it remains unclear whether Hcrt/Orx neurons are one homogeneous population, or whether there are several distinct types of Hcrt/Orx cells. Here, we collated diverse structural and functional information about individual Hcrt/Orx neurons in mouse brain slices, by combining patch-clamp analysis of spike firing, membrane currents and synaptic inputs with confocal imaging of cell shape and subsequent 3-dimensional Sholl analysis of dendritic architecture. Statistical cluster analysis of intrinsic firing properties revealed that Hcrt/Orx neurons fall into two distinct types. These two cell types also differ in the complexity of their dendritic arbour, the strength of AMPA and GABAA receptor-mediated synaptic drive that they receive, and the density of low-threshold, 4-aminopyridine-sensitive, transient K+ current. Our results provide quantitative evidence that, at the cellular level, the mouse Hcrt/Orx system is composed of two classes of neurons with different firing properties, morphologies and synaptic input organization.
authors.affiliation: Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schöne
authors.forename: Anne
authors.initials: A
authors.lastname: Venner
authors.forename: David
authors.initials: D
authors.lastname: Knowles
authors.forename: Mahesh M
authors.initials: MM
authors.lastname: Karnani
authors.forename: Denis
authors.initials: D
authors.lastname: Burdakov
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001921:Brain / Q000166:cytology*; D048430:Cell Shape / Q000502:physiology; D016000:Cluster Analysis; D003712:Dendrites / Q000502:physiology; D055724:Electrophysiological Phenomena / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D055369:Miniature Postsynaptic Potentials / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D000068797:Orexins; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism
chemical_list: D058787:GABA-A Receptor Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D024642:Potassium Channels, Voltage-Gated; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D015761:4-Aminopyridine