Targeted anatomical and functional identification of antinociceptive and pronociceptive serotonergic neurons that project to the spinal dorsal horn
Spinally projecting serotonergic neurons play a key role in controlling pain sensitivity and can either increase or decrease nociception depending on physiological context. It is currently unknown how serotonergic neurons mediate these opposing effects. Utilizing virus-based strategies and Tph2-Cre...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-02-01
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| Online Access: | https://elifesciences.org/articles/78689 |
| _version_ | 1828010421644165120 |
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| author | Robert Philip Ganley Marilia Magalhaes de Sousa Kira Werder Tugce Öztürk Raquel Mendes Matteo Ranucci Hendrik Wildner Hanns Ulrich Zeilhofer |
| author_facet | Robert Philip Ganley Marilia Magalhaes de Sousa Kira Werder Tugce Öztürk Raquel Mendes Matteo Ranucci Hendrik Wildner Hanns Ulrich Zeilhofer |
| author_sort | Robert Philip Ganley |
| collection | DOAJ |
| description | Spinally projecting serotonergic neurons play a key role in controlling pain sensitivity and can either increase or decrease nociception depending on physiological context. It is currently unknown how serotonergic neurons mediate these opposing effects. Utilizing virus-based strategies and Tph2-Cre transgenic mice, we identified two anatomically separated populations of serotonergic hindbrain neurons located in the lateral paragigantocellularis (LPGi) and the medial hindbrain, which respectively innervate the superficial and deep spinal dorsal horn and have contrasting effects on sensory perception. Our tracing experiments revealed that serotonergic neurons of the LPGi were much more susceptible to transduction with spinally injected AAV2retro vectors than medial hindbrain serotonergic neurons. Taking advantage of this difference, we employed intersectional chemogenetic approaches to demonstrate that activation of the LPGi serotonergic projections decreases thermal sensitivity, whereas activation of medial serotonergic neurons increases sensitivity to mechanical von Frey stimulation. Together these results suggest that there are functionally distinct classes of serotonergic hindbrain neurons that differ in their anatomical location in the hindbrain, their postsynaptic targets in the spinal cord, and their impact on nociceptive sensitivity. The LPGi neurons that give rise to rather global and bilateral projections throughout the rostrocaudal extent of the spinal cord appear to be ideally poised to contribute to widespread systemic pain control. |
| first_indexed | 2024-04-10T08:54:23Z |
| format | Article |
| id | doaj.art-4ff23c7f706d407fb198f8d2ab0f17ca |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-10T08:54:23Z |
| publishDate | 2023-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4ff23c7f706d407fb198f8d2ab0f17ca2023-02-21T16:57:14ZengeLife Sciences Publications LtdeLife2050-084X2023-02-011210.7554/eLife.78689Targeted anatomical and functional identification of antinociceptive and pronociceptive serotonergic neurons that project to the spinal dorsal hornRobert Philip Ganley0https://orcid.org/0000-0001-8502-9870Marilia Magalhaes de Sousa1Kira Werder2Tugce Öztürk3Raquel Mendes4Matteo Ranucci5Hendrik Wildner6Hanns Ulrich Zeilhofer7Institute for Pharmacology and Toxicology, University of Zurich, Zurich, SwitzerlandInstitute for Pharmacology and Toxicology, University of Zurich, Zurich, SwitzerlandInstitute for Pharmacology and Toxicology, University of Zurich, Zurich, SwitzerlandInstitute for Pharmacology and Toxicology, University of Zurich, Zurich, SwitzerlandInstitute for Pharmacology and Toxicology, University of Zurich, Zurich, SwitzerlandInstitute for Pharmacology and Toxicology, University of Zurich, Zurich, SwitzerlandInstitute for Pharmacology and Toxicology, University of Zurich, Zurich, SwitzerlandInstitute for Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland; Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, Zurich, SwitzerlandSpinally projecting serotonergic neurons play a key role in controlling pain sensitivity and can either increase or decrease nociception depending on physiological context. It is currently unknown how serotonergic neurons mediate these opposing effects. Utilizing virus-based strategies and Tph2-Cre transgenic mice, we identified two anatomically separated populations of serotonergic hindbrain neurons located in the lateral paragigantocellularis (LPGi) and the medial hindbrain, which respectively innervate the superficial and deep spinal dorsal horn and have contrasting effects on sensory perception. Our tracing experiments revealed that serotonergic neurons of the LPGi were much more susceptible to transduction with spinally injected AAV2retro vectors than medial hindbrain serotonergic neurons. Taking advantage of this difference, we employed intersectional chemogenetic approaches to demonstrate that activation of the LPGi serotonergic projections decreases thermal sensitivity, whereas activation of medial serotonergic neurons increases sensitivity to mechanical von Frey stimulation. Together these results suggest that there are functionally distinct classes of serotonergic hindbrain neurons that differ in their anatomical location in the hindbrain, their postsynaptic targets in the spinal cord, and their impact on nociceptive sensitivity. The LPGi neurons that give rise to rather global and bilateral projections throughout the rostrocaudal extent of the spinal cord appear to be ideally poised to contribute to widespread systemic pain control.https://elifesciences.org/articles/78689painserotoninhindbrainprojection neuronspinal cord |
| spellingShingle | Robert Philip Ganley Marilia Magalhaes de Sousa Kira Werder Tugce Öztürk Raquel Mendes Matteo Ranucci Hendrik Wildner Hanns Ulrich Zeilhofer Targeted anatomical and functional identification of antinociceptive and pronociceptive serotonergic neurons that project to the spinal dorsal horn eLife pain serotonin hindbrain projection neuron spinal cord |
| title | Targeted anatomical and functional identification of antinociceptive and pronociceptive serotonergic neurons that project to the spinal dorsal horn |
| title_full | Targeted anatomical and functional identification of antinociceptive and pronociceptive serotonergic neurons that project to the spinal dorsal horn |
| title_fullStr | Targeted anatomical and functional identification of antinociceptive and pronociceptive serotonergic neurons that project to the spinal dorsal horn |
| title_full_unstemmed | Targeted anatomical and functional identification of antinociceptive and pronociceptive serotonergic neurons that project to the spinal dorsal horn |
| title_short | Targeted anatomical and functional identification of antinociceptive and pronociceptive serotonergic neurons that project to the spinal dorsal horn |
| title_sort | targeted anatomical and functional identification of antinociceptive and pronociceptive serotonergic neurons that project to the spinal dorsal horn |
| topic | pain serotonin hindbrain projection neuron spinal cord |
| url | https://elifesciences.org/articles/78689 |
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