Substance P-expressing Neurons in the Superficial Dorsal Horn of the Mouse Spinal Cord: Insights into Their Functions and their Roles in Synaptic Circuits
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The tachykinin peptide substance P (SP) is expressed by many interneurons and some projection neurons in the superficial dorsal horn of the spinal cord. We have recently shown that SP-expressing excitatory interneurons in lamina II correspond largely to a morphological class known as radial cells. However, little is known about their function, or their synaptic connectivity. Here we use a modification of the Brainbow technique to define the excitatory synaptic input to SP radial cells. We show that around half of their excitatory synapses (identified by expression of Homer) are from boutons with VGLUT2, which are likely to originate mainly from local interneurons. The remaining synapses presumably include primary afferents, which generally have very low levels of VGLUT2. Our results also suggest that the SP cells are preferentially innervated by a population of excitatory interneurons defined by expression of green fluorescent protein under control of the gene for gastrin-releasing peptide, and that they receive sparser input from other types of excitatory interneuron. We show that around 40% of lamina I projection neurons express Tac1, the gene encoding substance P. Finally, we show that silencing Tac1-expressing cells in the dorsal horn results in a significant reduction in reflex responses to cold and radiant heat, but does not affect withdrawal to von Frey hairs, or chloroquine-evoked itch.
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The Sox5 dorsal excitatory family comprised Excit-14, Excit-15, Excit-16, Excit-17, Excit-18, and Excit-19 and expressed markers suggestive of a role in coping pain and mechanical nociception.
“The Sox5 dorsal, the excitatory family was comprised of Excit-14, Excit-15, Excit-16, Excit-17, Excit-18, and Excit-19, and expressed markers suggestive of a role in coping pain and mechanical nociception46,52,56,63–67.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [66]
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- Authors
- Polgár, E., Bell, A. M., Gutierrez-Mecinas, M., Dickie, A. C., Akar, O., Costreie, M., Watanabe, M., & Todd, A. J.
- Affiliations
- University of Glasgow (GB)
- Hokkaido University (JP)
- Corresponding author
- Todd, Andrew J.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 450
- Pages
- 113-125
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC7717171
- OpenAlex
- W3038339263
- Cited by
- 19
- References
- 59
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 1
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Funders
- Medical Research Council (MR/S002987/1)
- Biotechnology and Biological Sciences Research Council (BB/N006119/1)
- Wellcome Trust (102645/Z/13/Z, 219433/Z/19/Z)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- substance P, TAC1, superficial dorsal horn, spinal interneurons, radial cell, lamina II, excitatory synaptic input, VGLUT2, Homer, gastrin-releasing peptide, projection neurons, pruritus, synaptic circuits, tachykinins
- MeSH terms
- Animals, Interneurons, Neurons, Spinal Cord, Substance P, Gastrin-Releasing Peptide, Posterior Horn Cells, Mice, Spinal Cord Dorsal Horn
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