- Title
- Calretinin-expressing islet cells are a source of pre- and post-synaptic inhibition of non-peptidergic nociceptor input to the mouse spinal cord
- Creator
- Davis, Olivia C.; Dickie, Allen C.; Mustapa, Marami B.; Boyle, Kieran A.; Browne, Tyler J.; Gradwell, Mark A.; Smith, Kelly M.; Polgár, Erika; Bell, Andrew M.; Kókai, Éva; Watanabe, Masahiko; Wildner, Hendrik; Zeilhofer, Hanns Ulrich; Ginty, David D.; Callister, Robert J.; Graham, Brett A.; Todd, Andrew J.; Hughes, David I.
- Relation
- NHMRC.1043933 http://purl.org/au-research/grants/nhmrc/1043933 | NHMRC|631000 http://purl.org/au-research/grants/nhmrc/631000
- Relation
- Scientific Reports Vol. 13, no. 11561
- Publisher Link
- http://dx.doi.org/10.1038/s41598-023-38605-9
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2023
- Description
- Unmyelinated non-peptidergic nociceptors (NP afferents) arborise in lamina II of the spinal cord and receive GABAergic axoaxonic synapses, which mediate presynaptic inhibition. However, until now the source of this axoaxonic synaptic input was not known. Here we provide evidence that it originates from a population of inhibitory calretinin-expressing interneurons (iCRs), which correspond to lamina II islet cells. The NP afferents can be assigned to 3 functionally distinct classes (NP1-3). NP1 afferents have been implicated in pathological pain states, while NP2 and NP3 afferents also function as pruritoceptors. Our findings suggest that all 3 of these afferent types innervate iCRs and receive axoaxonic synapses from them, providing feedback inhibition of NP input. The iCRs also form axodendritic synapses, and their targets include cells that are themselves innervated by the NP afferents, thus allowing for feedforward inhibition. The iCRs are therefore ideally placed to control the input from non-peptidergic nociceptors and pruritoceptors to other dorsal horn neurons, and thus represent a potential therapeutic target for the treatment of chronic pain and itch.
- Subject
- calretinin-expressing interneurons; islet cells; synapses; mice; treatment; chronic pain
- Identifier
- http://hdl.handle.net/1959.13/1492282
- Identifier
- uon:53289
- Identifier
- ISSN:2045-2322
- Rights
- © The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
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