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Excitation of cortical nNOS/NK1R neurons by hypocretin 1 is independent of sleep homeostasis.
Cereb. Cortex 29, 1090-1108 (2019)
We have proposed that cortical nNOS/NK1R interneurons have a role in sleep homeostasis. The hypocretins (orexins) are wake-promoting neuropeptides and hypocretin/orexin (Hcrt) neurons project to the cortex. Hcrt peptides affect deep layer cortical neurons, and Hcrt receptor 1 (Hcrtr1; Ox1r) mRNA is expressed in cortical nNOS/NK1R cells. Therefore, we investigated whether Hcrt neuron stimulation affects cingulate cortex nNOS/NK1R neurons. Bath application of HCRT1/orexin-A evoked an inward current and membrane depolarization in most nNOS/NK1R cells which persisted in tetrodotoxin; optogenetic stimulation of Hcrt terminals expressing channelrhodopsin-2 confirmed these results, and pharmacological studies determined that HCRTR1 mediated these responses. Single-cell RT-PCR found Hcrtr1 mRNA in 31% of nNOS/NK1R cells without any Hcrtr2 mRNA expression; immunohistochemical studies of Hcrtr1-EGFP mice confirmed that a minority of nNOS/NK1R cells express HCRTR1. When Hcrt neurons degenerated in orexin-tTA;TetO DTA mice, the increased EEG delta power during NREM sleep produced in response to 4 h sleep deprivation and c-FOS expression in cortical nNOS/NK1R cells during recovery sleep were indistinguishable from that of controls. We conclude that Hcrt excitatory input to these deep layer cells is mediated through HCRTR1 but is unlikely to be involved in the putative role of cortical nNOS/NK1R neurons in sleep homeostasis.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Arousal ; Hypocretin ; Nitric Oxide ; Sleep ; Wakefulness; Orexin Neurons; Orexin/hypocretin Neurons; Gabaergic Neurons; Promotes Sleep; Brain-stem; Narcolepsy; Cortex; Activation; Cataplexy; Classification
Language
english
Publication Year
2019
Prepublished in Year
2018
HGF-reported in Year
2018
ISSN (print) / ISBN
1047-3211
e-ISSN
1460-2199
Journal
Cerebral Cortex
Quellenangaben
Volume: 29,
Issue: 3,
Pages: 1090-1108
Publisher
Oxford University Press
Publishing Place
Journals Dept, 2001 Evans Rd, Cary, Nc 27513 Usa
Reviewing status
Peer reviewed
Institute(s)
Institute of Neurogenomics (ING)
POF-Topic(s)
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-503290-001
WOS ID
WOS:000462494100013
PubMed ID
29462275
Erfassungsdatum
2018-12-20