Spinal Inhibitory Ptf1a-Derived Neurons Prevent Self-Generated Itch
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Abstract
Chronic itch represents an incapacitating burden on patients suffering from a spectrum of diseases. Despite recent advances in our understanding of the cells and circuits implicated in the processing of itch information, chronic itch often presents itself without an apparent cause. Here, we identify a spinal subpopulation of inhibitory neurons defined by the expression of Ptf1a, involved in gating mechanosensory information self-generated during movement. These neurons receive tactile and motor input and establish presynaptic inhibitory contacts on mechanosensory afferents. Loss of Ptf1a neurons leads to increased hairy skin sensitivity and chronic itch, partially mediated by the classic itch pathway involving gastrin-releasing peptide receptor (GRPR) spinal neurons. Conversely, chemogenetic activation of GRPR neurons elicits itch, which is suppressed by concomitant activation of Ptf1a neurons. These findings shed light on the circuit mechanisms implicated in chronic itch and open novel targets for therapy developments.
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A subset of cells from the dorsal dI4.6/dI6 lineages contributed to most ventral inhibitory populations.
“A subset of cells from the dorsal dI4.6/dI6 lineages contributed to most ventral inhibitory populations, which was unexpected though there have been reports of scattered dI4 Ptf1a-derived cells in the embryonic and perinatal ventral horn103,104, and the very small dI6 population is known to be ventrally located105–107.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [104]
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Internal and External Feedback Circuits for Skilled Forelimb MovementPreprint
Azim, E., Fink, A. J. P., & Jessell, T. M. (2014) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2014.79.024786 · Cited by 37 · 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
Neuropeptide Y in itch regulation
Jakobsson, J. E. T., Ma, H., & Lagerström, M. C. (2019) · Neuropeptides · doi:10.1016/j.npep.2019.101976 · Cited by 20 · see citing works
Acute and Chronic Tactile Sensory Testing after Spinal Cord Injury in Rats
Detloff, M. R., Fisher, L. C., Deibert, R. J., et al. (2012) · Journal of Visualized Experiments · doi:10.3791/3247-v · Cited by 15 · see citing works
Tripathi, R., Knusel, K. D., Ezaldein, H. H., et al. (2018) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2018.10.025 · Cited by 11 · see citing works
Good vibrations: Itch induction by whole body vibration exercise without the need of a pruritogen
Mueller, S. M., Fischer, M., Herger, S., et al. (2018) · Experimental Dermatology · doi:10.1111/exd.13776 · Cited by 7 · see citing works
Babayan, B. M., & Konen, C. S. (2019) · Neuron · doi:10.1016/j.neuron.2019.09.034 · Cited by 7 · see citing works
Counter-stimuli Inhibit GRPR Neurons via GABAergic Signaling in the Spinal CordPreprint
Bardoni, R., Barry, D. M., Li, H., Shen, K., Jeffry, J. A., Yang, Q., Comitato, A., Li, Y.-Q., & Chen, Z. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/489831 · Cited by 5 · see citing works
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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
- Authors
- Escalante, A., & Klein, R.
- Affiliations
- Max Planck Institute of Neurobiology (DE)
- Corresponding author
- Escalante, Augusto
- Klein, Rüdiger
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 33
- Issue
- 8
- Pages
- 108422
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W3107880009
- Cited by
- 17
- References
- 100
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 2 · 2020: 1
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by-nc-nd)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Max-Planck-Gesellschaft
- “la Caixa” Foundation
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- chronic pruritus, Ptf1a, gastrin-releasing peptide receptor, tactile sensitivity, chemogenetic activation
- MeSH terms
- Animals, DNA-Binding Proteins, Humans, Neurons, Pruritus, Transcription Factors, 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 ›
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