Expression of green fluorescent protein defines a specific population of lamina II excitatory interneurons in the GRP::eGFP mouse
Open accessAbstract
Dorsal horn excitatory interneurons that express gastrin-releasing peptide (GRP) are part of the circuit for pruritogen-evoked itch. They have been extensively studied in a transgenic line in which enhanced green fluorescent protein (eGFP) is expressed under control of the Grp gene. The GRP-eGFP cells are separate from several other neurochemically-defined excitatory interneuron populations, and correspond to a class previously defined as transient central cells. However, mRNA for GRP is widely distributed among excitatory interneurons in superficial dorsal horn. Here we show that although Grp mRNA is present in several transcriptomically-defined populations, eGFP is restricted to a discrete subset of cells in the GRP::eGFP mouse, some of which express the neuromedin receptor 2 and likely belong to a cluster defined as Glut8. We show that these cells receive much of their excitatory synaptic input from MrgA3/MrgD-expressing nociceptive/pruritoceptive afferents and C-low threshold mechanoreceptors. Although the cells were not innervated by pruritoceptors expressing brain natriuretic peptide (BNP) most of them contained mRNA for NPR1, the receptor for BNP. In contrast, these cells received only ~ 10% of their excitatory input from other interneurons. These findings demonstrate that the GRP-eGFP cells constitute a discrete population of excitatory interneurons with a characteristic pattern of synaptic input.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The Reln dorsal excitatory family comprised Excit-8, Excit-9, Excit-10, and Excit-11 and expressed markers indicative of a role in chemical itch sensation.
“The Reln dorsal, excitatory family was comprised of Excit-8, Excit-9, Excit-10, and Excit-11 and expressed markers indicative of a role in chemical itch sensation58–62.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [58]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Molecular Architecture of the Mouse Nervous System
Zeisel, A., Hochgerner, H., Lönnerberg, P., Johnsson, A., Memic, F., van der Zwan, J., Häring, M., Braun, E., Borm, L. E., La Manno, G., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.021 · Cited by 2,995 · see citing works
Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing
Usoskin, D., Furlan, A., Islam, S., Abdo, H., Lönnerberg, P., Lou, D., Hjerling-Leffler, J., Haeggström, J., Kharchenko, O., Kharchenko, P. V., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.3881 · Cited by 2,136 · see citing works
Abraira, V. E., & Ginty, D. D. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.051 · Cited by 1,648 · see citing works
Discriminative and affective touch: Sensing and feeling.
McGlone, F., Wessberg, J., & Olausson, H. (2014) · Neuron · doi:10.1016/j.neuron.2014.05.001 · Cited by 1,112 · see citing works
A gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord
Sun, Y.-G., & Chen, Z. (2007) · Nature · doi:10.1038/nature06029 · Cited by 792 · see citing works
Cavanaugh, D. J., Lee, H., Lo, L., Shields, S. D., Zylka, M. J., Basbaum, A. I., & Anderson, D. J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0901507106 · Cited by 706 · see citing works
A subpopulation of nociceptors specifically linked to itch
Han, L., Ma, C., Liu, Q., Weng, H.-J., Cui, Y., Tang, Z., Kim, Y., Nie, H., Qu, L., Patel, K., et al. (2012) · Nature Neuroscience · doi:10.1038/nn.3289 · Cited by 614 · see citing works
Cellular Basis of Itch Sensation
Sun, Y.-G., Zhao, Z.-Q., Meng, X.-L., Yin, J., Liu, X., & Chen, Z. (2009) · Science · doi:10.1126/science.1174868 · Cited by 612 · see citing works
The Cells and Circuitry for Itch Responses in Mice
Mishra, S. K., & Hoon, M. A. (2013) · Science · doi:10.1126/science.1233765 · Cited by 507 · see citing works
Häring, M., Zeisel, A., Hochgerner, H., Rinwa, P., Jakobsson, J. E. T., Lönnerberg, P., La Manno, G., Sharma, N., Borgius, L., Kiehn, O., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0141-1 · Cited by 470 · see citing works
Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors
Seal, R. P., Wang, X., Guan, Y., Raja, S. N., Woodbury, C. J., Basbaum, A. I., & Edwards, R. H. (2009) · Nature · doi:10.1038/nature08505 · Cited by 465 · see citing works
Todd, A. J., Hughes, D. I., Polgár, E., Nagy, G., Mackie, M., Ottersen, O. P., & Maxwell, D. J. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02406.x · Cited by 436 · see citing works
Self-citationThe Cellular and Synaptic Architecture of the Mechanosensory Dorsal Horn
Abraira, V. E., Kuehn, E. D., Chirila, A. M., Springel, M. W., Toliver, A. A., Zimmerman, A. L., Orefice, L. L., Boyle, K. A., Bai, L., Song, B. J., et al. (2017) · Cell · doi:10.1016/j.cell.2016.12.010 · Cited by 409 · see citing works
Self-citationGrudt, T. J., & Perl, E. R. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2001.012890 · Cited by 402 · see citing works
Sathyamurthy, A., Johnson, K. R., Matson, K. J. E., Dobrott, C. I., Li, L., Ryba, A. R., Bergman, T. B., Kelly, M. C., Kelley, M. W., & Levine, A. J. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.003 · Cited by 370 · see citing works
Bac to the future: The use of bac transgenic mice for neuroscience research
Heintz, N. (2001) · Nature reviews. Neuroscience · doi:10.1038/35104049 · Cited by 333 · see citing works
A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia
Lü, Y., Dong, H., Gao, Y., Gong, Y., Ren, Y., Gu, N., Zhou, S., Xia, N., Sun, Y., Ji, R., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci70026 · Cited by 287 · see citing works
Mechanisms of itch evoked by β-alanine
Liu, Q., Sikand, P., Ma, C., Tang, Z.-X., Han, L., Li, Z., Sun, S., LaMotte, R., & Dong, X.-Z. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.3509-12.2012 · Cited by 272 · see citing works
A central neural circuit for itch sensation
Mu, D., Deng, J., Liu, K., Wu, Z.-Y., Shi, Y.-F., Guo, W., Mao, Q.-Q., Liu, X., Li, H., & Sun, Y.-G. (2017) · Science · doi:10.1126/science.aaf4918 · Cited by 259 · see citing works
Circuit dissection of the role of somatostatin in itch and pain
Huang, J., Polgár, E., Solinski, H. J., Mishra, S. K., Tseng, P.-Y., Iwagaki, N., Boyle, K. A., Dickie, A. C., Kriegbaum, M. C., Wildner, H., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0119-z · Cited by 257 · see citing works
Self-citationLü, Y., & Perl, E. R. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0102-05.2005 · Cited by 255 · see citing works
Liu, Q., Vrontou, S., Rice, F. L., Zylka, M. J., Dong, X., & Anderson, D. J. (2007) · Nature Neuroscience · doi:10.1038/nn1937 · Cited by 227 · see citing works
Todd, A. J., Puskár, Z., SPIKE, R. C., Hughes, C., Watt, C., & Forrest, L. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-10-04103.2002 · Cited by 214 · see citing works
Self-citationIdentifying functional populations among the interneurons in laminae I-III of the spinal dorsal horn
Todd, A. J. (2017) · Molecular Pain · doi:10.1177/1744806917693003 · Cited by 204 · see citing works
Self-citationBrumovsky, P. R., Watanabe, M., & Hökfelt, T. G. M. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.02.068 · Cited by 164 · see citing works
Self-citationLeaky Gate Model: Intensity-Dependent Coding of Pain and Itch in the Spinal Cord
Sun, S., Xu, Q., Guo, C., Guan, Y., Liu, Q., & Dong, X. (2017) · Neuron · doi:10.1016/j.neuron.2017.01.012 · Cited by 154 · see citing works
Qu, L., Fan, N., Ma, C., et al. (2014) · Brain · doi:10.1093/brain/awu007 · Cited by 119 · see citing works
How Gastrin-Releasing Peptide Opens the Spinal Gate for Itch
Pagani, M., Albisetti, G. W., Sivakumar, N., Wildner, H., Santello, M., Johannssen, H. C., & Zeilhofer, H. U. (2019) · Neuron · doi:10.1016/j.neuron.2019.04.022 · Cited by 114 · see citing works
Self-citationFleming, M. S., Ramos, D., Han, S. B., et al. (2012) · Molecular Pain · doi:10.1186/1744-8069-8-52 · Cited by 104 · see citing works
A central role for spinal dorsal horn neurons that express neurokinin-1 receptors in chronic itch
Akiyama, T., Nguyen, T., Curtis, E., Nishida, K., Devireddy, J., Delahanty, J., Carstens, M. I., & Carstens, E. E. (2015) · Pain · doi:10.1097/j.pain.0000000000000172 · Cited by 103 · see citing works
Differential Coding of Itch and Pain by a Subpopulation of Primary Afferent Neurons
Sharif, B., Ase, A. R., Ribeiro‐da‐Silva, A., & Séguéla, P. (2020) · Neuron · doi:10.1016/j.neuron.2020.03.021 · Cited by 102 · see citing works
Solórzano, C., Villafuerte, D. B., Meda, K., Cevikbas, F., Braz, J. M., Sharif‐Naeini, R., Juarez-Salinas, D. L., Llewellyn‐Smith, I. J., Guan, Z., & Basbaum, A. I. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.2955-14.2015 · Cited by 89 · see citing works
Dorsal Horn Gastrin-Releasing Peptide Expressing Neurons Transmit Spinal Itch But Not Pain Signals
Albisetti, G. W., Pagani, M., Platonova, E., Hösli, L., Johannssen, H. C., Fritschy, J., Wildner, H., & Zeilhofer, H. U. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.2559-18.2019 · Cited by 87 · see citing works
Self-citationBarry, D. M., Liu, X., Liu, B., Liu, X., Gao, F., Zeng, X., Liu, J., Yang, Q., Wilhelm, S. J., Yin, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15230-y · Cited by 84 · see citing works
Gutierrez-Mecinas, M., Furuta, T., Watanabe, M., & Todd, A. J. (2016) · Molecular Pain · doi:10.1177/1744806916629065 · Cited by 81 · see citing works
Self-citationStructural basis for the hijacking of endosomal sorting nexin proteins by Chlamydia trachomatis
Paul, B., Kim, H. S., Kerr, M. C., Huston, W. M., Teasdale, R. D., & Collins, B. M. (2017) · eLife · doi:10.7554/elife.22311 · Cited by 81 · see citing works
Mechanically evoked itch in humans
Fukuoka, M., Miyachi, Y., & Ikoma, A. (2013) · Pain · doi:10.1016/j.pain.2013.02.021 · Cited by 72 · see citing works
Zeng, H., Gragerov, A., Hohmann, J. G., Pavlova, M. N., Schimpf, B. A., Xu, H., Wu, L., Toyoda, H., Zhao, M., Rohde, A. D., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01148-06 · Cited by 72 · see citing works
Gutièrrez‐Mecinas, M., Bell, A. M., Marin, A., Taylor, R., Boyle, K. A., Furuta, T., Watanabe, M., Polgár, E., & Todd, A. J. (2016) · Pain · doi:10.1097/j.pain.0000000000000778 · Cited by 72 · see citing works
Self-citationDickie, A. C., Bell, A. M., Iwagaki, N., Polgár, E., Gutièrrez‐Mecinas, M., Kelly, R., Lyon, H., Turnbull, K., West, S. J., Etlin, A., et al. (2018) · Pain · doi:10.1097/j.pain.0000000000001406 · Cited by 72 · see citing works
Self-citationSparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors
Olson, W. P., Abdus-Saboor, I., Cui, L., Burdge, J., Raabe, T. D., Ma, M., & Luo, W. (2017) · eLife · doi:10.7554/elife.29507 · Cited by 67 · see citing works
Goswami, S. C., Thierry-Mieg, D., Thierry-Mieg, J., Mishra, S., Hoon, M., Mannes, A., & Iadarola, M. (2014) · Molecular Pain · doi:10.1186/1744-8069-10-44 · Cited by 65 · see citing works
Sukhtankar, D. D., & Ko, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067422 · Cited by 60 · see citing works
Albisetti, G. W., Ghanem, A., Foster, E., Conzelmann, K., Zeilhofer, H. U., & Wildner, H. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.1277-17.2017 · Cited by 52 · see citing works
Self-citationKoga, K., Yamagata, R., Kohno, K., Yamane, T., Shiratori‐Hayashi, M., Kohro, Y., Tozaki‐Saitoh, H., & Tsuda, M. (2019) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2019.09.034 · Cited by 51 · see citing works
Schiff, N. D. (2020) · Neuron · doi:10.1016/j.neuron.2020.02.016 · Cited by 49 · see citing works
Torres, R., Croll, S. D., Vercollone, J., Reinhardt, J., Griffiths, J., Zabski, S. M., Anderson, K. D., Adams, N. C., Gowen, L. C., Sleeman, M. W., et al. (2007) · Pain · doi:10.1016/j.pain.2007.01.036 · Cited by 46 · see citing works
Gutièrrez‐Mecinas, M., Kuehn, E. D., Abraira, V. E., Polgár, E., Watanabe, M., & Todd, A. J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.05.009 · Cited by 44 · see citing works
Self-citationGutièrrez‐Mecinas, M., Watanabe, M., & Todd, A. J. (2014) · Molecular Pain · doi:10.1186/1744-8069-10-79 · Cited by 42 · see citing works
Self-citationSpinal somatostatin-positive interneurons transmit chemical itch
Fatima, M., Ren, X., Pan, H., Slade, H. F. E., Asmar, A. J., Xiong, C. M., Shi, A., Xiong, A. E., Wang, L., & Duan, B. (2019) · Pain · doi:10.1097/j.pain.0000000000001499 · Cited by 41 · see citing works
Expression of cholecystokinin by neurons in mouse spinal dorsal horn
Gutièrrez‐Mecinas, M., Bell, A. M., Shepherd, F., Polgár, E., Watanabe, M., Furuta, T., & Todd, A. J. (2019) · The Journal of Comparative Neurology · doi:10.1002/cne.24657 · Cited by 41 · see citing works
Self-citationGutièrrez‐Mecinas, M., Bell, A. M., Polgár, E., Watanabe, M., & Todd, A. J. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.08.013 · Cited by 38 · see citing works
Self-citationLarsson, M., & Broman, J. (2019) · eNeuro · doi:10.1523/eneuro.0007-19.2019 · Cited by 37 · see citing works
Taylor‐Blake, B., & Zylka, M. J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008674 · Cited by 35 · see citing works
Koizumi, A., Zhan, M., Ban, H., Kida, I., Martino, F. D., Vaessen, M. J., de Gelder, B., & Amano, K. (2019) · eNeuro · doi:10.1523/eneuro.0429-19.2019 · Cited by 34 · see citing works
GRPR/PI3Kγ: Partners in Central Transmission of Itch
Pereira, P. J. S., Machado, G. D. B., Danesi, G. M., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.2310-15.2015 · Cited by 33 · see citing works
Staley, K. J., & Módy, I. (1991) · Synapse · doi:10.1002/syn.890090308 · Cited by 28 · see citing works
Sikandar, S., West, S. J., McMahon, S. B., Bennett, D., & Dickenson, A. H. (2017) · Physiological Reports · doi:10.14814/phy2.13323 · Cited by 25 · see citing works
Self-citationPolgár, 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-citationSparse genetic tracing reveals regionally specific functional organization of mammalian nociceptorsPreprint
Olson, W. P., Abdus-Saboor, I., Cui, L., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/149641 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Mechanical Allodynia Circuitry in the Dorsal Horn Is Defined by the Nature of the Injury
Peirs, C., Williams, S.-P. G., Zhao, X., Arokiaraj, C. M., Ferreira, D. W., Noh, M.-C., Smith, K. M., Halder, P., Corrigan, K. A., Gedeon, J. Y., et al. (2021) · Neuron · doi:10.1016/j.neuron.2020.10.027 · Cited by 190 · 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
- Bell, A. M., Gutierrez-Mecinas, M., Stevenson, A., Casas-Benito, A., Wildner, H., West, S. J., Watanabe, M., & Todd, A. J.
- Affiliations
- University of Glasgow (GB)
- University of Zurich (CH)
- John Radcliffe Hospital (GB)
- Hokkaido University (JP)
- Corresponding author
- Bell, Andrew M.
- Todd, Andrew J.
- Venue
- Scientific Reports
- Published
- 2020-08-06
- Volume
- 10
- Issue
- 1
- Pages
- 13176-13176
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7411045
- OpenAlex
- W3047547106
- Cited by
- 25
- References
- 60
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 4 · 2022: 5 · 2021: 7 · 2020: 2
- FWCI
- 2.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
- ETH Zürich Research Collection (cc-by)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Wellcome Trust (102645)
- Medical Research Council (MR/S002987/1)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- gastrin-releasing peptide, lamina II, GLUT8, brain natriuretic peptide, NPR1, pruritus, synaptic input
- MeSH terms
- Animals, Interneurons, Substantia Gelatinosa, Synapses, Gene Expression, Green Fluorescent Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review