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 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.
Sakurai
Takeshi
T
Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan. stakeshi@md.tsukuba.ac.jp
Nagata
Ruby
R
Yamanaka
Akihiro
A
Kawamura
Hiroko
H
Tsujino
Natsuko
N
Muraki
Yo
Y
Kageyama
Haruaki
H
Kunita
Satoshi
S
Takahashi
Satoru
S
Goto
Katsutoshi
K
Koyama
Yoshimasa
Y
Shioda
Seiji
S
Yanagisawa
Masashi
M
D000818:Animals; D001933:Brain Stem / Q000033:anatomy & histology / Q000187:drug effects / Q000648:ultrastructure; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007031:Hypothalamus / Q000033:anatomy & histology* / Q000187:drug effects / Q000648:ultrastructure; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000033:anatomy & histology* / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism*; D000068797:Orexins; D018408:Patch-Clamp Techniques; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013779:Tetrodotoxin / Q000235:genetics; D014851:Wakefulness / Q000502:physiology
D018679:Cholinergic Agonists; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D013779:Tetrodotoxin; D002217:Carbachol