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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.
Pubmed ID: 29462275 RIS Download
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This polyclonal targets nNOS (neuronal) antibody
View all literature mentionsThis polyclonal targets peptide mapping at the C-terminus of human Orexin-A
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal targets FOS
View all literature mentionsThis polyclonal targets IgY (IgG) (H+L)
View all literature mentionsMus musculus with name STOCK Tg(Hcrtr1-EGFP)KP68Gsat/Mmucd from MMRRC.
View all literature mentionsMus musculus with name B6;129S-Nos1tm1.1(cre/ERT2)Zjh/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J from IMSR.
View all literature mentionsMus musculus with name B6;129S-Nos1tm1.1(cre/ERT2)Zjh/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis polyclonal targets nNOS (neuronal) antibody
View all literature mentionsThis polyclonal targets peptide mapping at the C-terminus of human Orexin-A
View all literature mentionsThis polyclonal targets peptide mapping at the C-terminus of human Orexin-A
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis polyclonal targets nNOS (neuronal) antibody
View all literature mentionsThis polyclonal targets nNOS (neuronal) antibody
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis polyclonal targets nNOS (neuronal) antibody
View all literature mentionsThis polyclonal targets peptide mapping at the C-terminus of human Orexin-A
View all literature mentionsThis polyclonal targets nNOS (neuronal) antibody
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis polyclonal targets peptide mapping at the C-terminus of human Orexin-A
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis polyclonal targets peptide mapping at the C-terminus of human Orexin-A
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis polyclonal targets nNOS (neuronal) antibody
View all literature mentionsMus musculus with name STOCK Tg(Hcrtr1-EGFP)KP68Gsat/Mmucd from MMRRC.
View all literature mentionsMus musculus with name B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J from IMSR.
View all literature mentionsMus musculus with name B6;129S-Nos1tm1.1(cre/ERT2)Zjh/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name STOCK Tg(Hcrtr1-EGFP)KP68Gsat/Mmucd from MMRRC.
View all literature mentionsMus musculus with name B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J from IMSR.
View all literature mentionsMus musculus with name B6;129S-Nos1tm1.1(cre/ERT2)Zjh/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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