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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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4-Aminopyridine / pharmacology
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Action Potentials / physiology
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Animals
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Brain / cytology*
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Cell Shape / physiology
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Cluster Analysis
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Dendrites / physiology
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Electrophysiological Phenomena / physiology*
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Excitatory Postsynaptic Potentials / physiology
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GABA-A Receptor Antagonists / pharmacology
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Green Fluorescent Proteins / genetics
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Inhibitory Postsynaptic Potentials / physiology
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Mice
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Mice, Transgenic
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Miniature Postsynaptic Potentials / physiology
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Neurons / cytology*
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Neurons / physiology*
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Neuropeptides / genetics
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Neuropeptides / metabolism*
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Orexins
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Patch-Clamp Techniques
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Potassium Channels, Voltage-Gated / antagonists & inhibitors
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Potassium Channels, Voltage-Gated / metabolism
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Promoter Regions, Genetic / genetics
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Receptors, AMPA / antagonists & inhibitors
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Receptors, AMPA / metabolism
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Receptors, GABA-A / metabolism
Substances
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GABA-A Receptor Antagonists
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Intracellular Signaling Peptides and Proteins
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Neuropeptides
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Orexins
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Potassium Channels, Voltage-Gated
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Receptors, AMPA
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Receptors, GABA-A
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enhanced green fluorescent protein
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Green Fluorescent Proteins
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4-Aminopyridine