Cortical nNOS neurons co-express the NK1 receptor and are depolarized by Substance P in multiple mammalian species
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We have previously demonstrated that Type I neuronal nitric oxide synthase (nNOS)-expressing neurons are sleep-active in the cortex of mice, rats, and hamsters. These neurons are known to be GABAergic, to express Neuropeptide Y (NPY) and, in rats, to co-express the Substance P (SP) receptor NK1, suggesting a possible role for SP in sleep/wake regulation. To evaluate the degree of co-expression of nNOS and NK1 in the cortex among mammals, we used double immunofluorescence for nNOS and NK1 and determined the anatomical distribution in mouse, rat, and squirrel monkey cortex. Type I nNOS neurons co-expressed NK1 in all three species although the anatomical distribution within the cortex was species-specific. We then performed in vitro patch clamp recordings in cortical neurons in mouse and rat slices using the SP conjugate tetramethylrhodamine-SP (TMR-SP) to identify NK1-expressing cells and evaluated the effects of SP on these neurons. Bath application of SP (0.03-1 μM) resulted in a sustained increase in firing rate of these neurons; depolarization persisted in the presence of tetrodotoxin. These results suggest a conserved role for SP in the regulation of cortical sleep-active neurons in mammals.
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The neocortex contains long-range GABAergic projection neurons that express SST, are most abundant in deep layers, project to other neocortical regions, have adapting and irregular spiking, frequently co-express NOS, Chodl, and NPY, and are active during sleep.
“the neocortex contains a population of long-range GABAergic projection neuron that express SST. These cells are most abundant in deep layers and project to other regions of the neocortex.”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Dittrich et al., 2012
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References 81 · Cited by 47
Research works printed but not linked: 1
- McConalogue K. Corvera C. U. Gamp P. D. Grady E. F. Bunnett N. W. (1998). Desensitization of the neurokinin-1 receptor (NK1-R) in neurons: effects of substance P on the distribution of NK1-R, Galphaq/11, G-protein receptor kinase-2/3, and beta-arrestin-1/2. Mol. Biol. Cell 9, 2305– 2324 9693383 PMC25486
- Authors
- Dittrich, L., Heiss, J. E., Warrier, D. R., Perez, X. A., Quik, M., & Kilduff, T. S.
- Affiliations
- SRI International (US)
- Corresponding author
- Dittrich, Lars
- Venue
- Frontiers in Neural Circuits
- Publisher
- Frontiers Media SA
- Published
- 2012
- Volume
- 6
- Pages
- 31-31
- ISSN
- 1662-5110 (ISSN-L)
- PMC
- PMC3367498
- OpenAlex
- W2152569254
- Cited by
- 47
- References
- 81
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 3 · 2023: 2 · 2022: 5 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 3 · 2016: 2 · 2014: 5 · 2013: 2 · 2012: 1
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Frontiers in Neural Circuits (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Tobacco-Related Disease Research Program
- University of California
- Deutsche Forschungsgemeinschaft (1718/1-1)
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL059658)
- National Institute of Neurological Disorders and Stroke (R01NS059910)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- neuronal nitric oxide synthase, neurokinin-1 receptor, substance P, cortical neurons, sleep-wake regulation, species differences, GABAergic neurons, neuropeptide Y
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