Substance P-expressing excitatory interneurons in the mouse superficial dorsal horn provide a propriospinal input to the lateral spinal nucleus
Open accessAbstract
The superficial dorsal horn (laminae I and II) of the spinal cord contains numerous excitatory and inhibitory interneurons, and recent studies have shown that each of these groups can be divided into several neurochemically distinct populations. Although it has long been known that some neurons in this region have intersegmental (propriospinal) axonal projections, there have been conflicting reports concerning the number of propriospinal cells and the extent of their axons. In addition, little is known about the neurochemical phenotype of propriospinal neurons or about the termination pattern of their axons. In the present study we show, using retrograde tracing, that around a third of lamina I-II neurons in the lumbar enlargement project at least five segments cranially. Substance P-expressing excitatory neurons are over-represented among these cells, accounting for one-third of the propriospinal neurons. In contrast, inhibitory interneurons and excitatory PKCγ neurons are both under-represented among the retrogradely labelled cells. By combining viral vector-mediated Cre-dependent anterograde tracing with immunocytochemistry, we provide evidence that the lateral spinal nucleus (LSN), rather than the superficial dorsal horn, is the main target for axons belonging to propriospinal substance P-expressing neurons. These findings help to resolve the discrepancies between earlier studies and have implications for the role of the LSN in pain mechanisms.
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The Rorb and Adamts5 dorsal inhibitory family comprised Inhib-1, Inhib-2, Inhib-3, Inhib-4, and Inhib-5, with markers of neurons involved in dampening of dynamic touch.
“The Rorb and Adamts5 dorsal, the inhibitory family was comprised of Inhib-1, Inhib-2, Inhib-3, Inhib-4, and Inhib-5, with markers of neurons involved in the dampening of dynamic touch48,68,69.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [69]
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- Bice TN Beal JA Quantitative and neurogenic analysis of the total population and subpopulations of neurons defined by axon projection in the superficial dorsal horn of the rat lumbar spinal cord J Comp Neurol 1997 388 4 550 564 10.1002/(SICI)1096-9861(19971201)388:4<550::AID-CNE4>3.0.CO;2-1 9388015 · DOI
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A harmonized atlas of mouse spinal cord cell types and their spatial organization
Russ, D. E., Cross, R. B. P., Li, L., Koch, S. C., Matson, K. J. E., Yadav, A., Alkaslasi, M. R., Lee, D. I., Le Pichon, C. E., Menon, V., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25125-1 · Cited by 255 · see citing works
Polgár, E., Bell, A. M., Gutierrez-Mecinas, M., Dickie, A. C., Akar, O., Costreie, M., Watanabe, M., & Todd, A. J. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.06.038 · Cited by 19 · see citing works
Self-citation
- Authors
- Gutierrez-Mecinas, M., Polgár, E., Bell, A. M., Herau, M., & Todd, A. J.
- Affiliations
- University of Glasgow (GB)
- Corresponding author
- Todd, Andrew J.
- Venue
- Brain Structure and Function
- Published
- 2018-03-01
- Volume
- 223
- Issue
- 5
- Pages
- 2377-2392
- ISSN
- 1863-2653 (ISSN-L)
- 1863-2661
- PMC
- PMC5968060
- OpenAlex
- W2794189368
- Cited by
- 28
- References
- 51
- Citations by year
- 2026: 2 · 2025: 5 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 5 · 2018: 3
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain Structure and Function (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion, cc-by)
- Funders
- Biotechnology and Biological Sciences Research Council (N006119)
- Wellcome Trust (102645)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- substance P, excitatory interneurons, superficial dorsal horn, propriospinal neurons, lateral spinal nucleus, inhibitory interneurons, retrograde tracing, anterograde tracing, pain mechanisms
- MeSH terms
- Animals, Cholera Toxin, Female, Interneurons, Male, Mice, Transgenic, Nerve Net, Phosphopyruvate Hydratase, Protein Kinase C, Substance P, Transduction, Genetic, Microscopy, Confocal, Green Fluorescent Proteins, Mice, PAX2 Transcription Factor, Spinal Cord Dorsal Horn
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