Input of Orexin/Hypocretin Neurons Revealed by a Genetically Encoded Tracer in Mice

The finding of orexin/hypocretin deficiency in narcolepsy patients suggests that this hypothalamic neuropeptide plays a crucial role in regulating sleep/wakefulness states. However, very little is known about the synaptic input of orexin/hypocretin-producing neurons (orexin neurons). We applied a tr...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2005-04, Vol.46 (2), p.297-308
Main Authors: Sakurai, Takeshi, Nagata, Ruby, Yamanaka, Akihiro, Kawamura, Hiroko, Tsujino, Natsuko, Muraki, Yo, Kageyama, Haruaki, Kunita, Satoshi, Takahashi, Satoru, Goto, Katsutoshi, Koyama, Yoshimasa, Shioda, Seiji, Yanagisawa, Masashi
Format: Article
Language:English
Subjects:
Animals
Brain
Brain Stem - anatomy & histology
Brain Stem - drug effects
Brain Stem - ultrastructure
Carbachol - pharmacology
Cholinergic Agonists - pharmacology
Cytoplasm
Green Fluorescent Proteins - genetics
Humans
Hypothalamus - anatomy & histology
Hypothalamus - drug effects
Hypothalamus - ultrastructure
Immunohistochemistry
In Situ Hybridization
Intracellular Signaling Peptides and Proteins - metabolism
Mice
Mice, Transgenic
Microscopy
Neural networks
Neural Pathways - anatomy & histology
Neural Pathways - drug effects
Neurons
Neurons - cytology
Neurons - physiology
Neuropeptides - metabolism
Orexins
Patch-Clamp Techniques
Proteins
Recombinant Fusion Proteins - genetics
Rodents
Sleep disorders
Software
Tetrodotoxin - genetics
Wakefulness - physiology
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Summary:The finding of orexin/hypocretin deficiency in narcolepsy patients suggests that this hypothalamic neuropeptide plays a crucial role in regulating sleep/wakefulness states. However, very little is known about the synaptic input of orexin/hypocretin-producing neurons (orexin neurons). We applied a transgenic method to map upstream neuronal populations that have synaptic connections to orexin neurons and revealed that orexin neurons receive input from several brain areas. These include the amygdala, basal forebrain cholinergic neurons, GABAergic neurons in the preoptic area, and serotonergic neurons in the median/paramedian raphe nuclei. Monoamine-containing groups that are innervated by orexin neurons do not receive reciprocal connections, while cholinergic neurons in the basal forebrain have reciprocal connections, which might be important for consolidating wakefulness. Electrophysiological study showed that carbachol excites almost one-third of orexin neurons and inhibits a small population of orexin neurons. These neuroanatomical findings provide important insights into the neural pathways that regulate sleep/wakefulness states.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2005.03.010