Calretinin positive neurons form an excitatory amplifier network in the spinal cord dorsal horn
Nociceptive information is relayed through the spinal cord dorsal horn, a critical area in sensory processing. The neuronal circuits in this region that underpin sensory perception must be clarified to better understand how dysfunction can lead to pathological pain. This study used an optogenetic ap...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-11-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/49190 |
| _version_ | 1811181058723414016 |
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| author | Kelly M Smith Tyler J Browne Olivia C Davis A Coyle Kieran A Boyle Masahiko Watanabe Sally A Dickinson Jacqueline A Iredale Mark A Gradwell Phillip Jobling Robert J Callister Christopher V Dayas David I Hughes Brett A Graham |
| author_facet | Kelly M Smith Tyler J Browne Olivia C Davis A Coyle Kieran A Boyle Masahiko Watanabe Sally A Dickinson Jacqueline A Iredale Mark A Gradwell Phillip Jobling Robert J Callister Christopher V Dayas David I Hughes Brett A Graham |
| author_sort | Kelly M Smith |
| collection | DOAJ |
| description | Nociceptive information is relayed through the spinal cord dorsal horn, a critical area in sensory processing. The neuronal circuits in this region that underpin sensory perception must be clarified to better understand how dysfunction can lead to pathological pain. This study used an optogenetic approach to selectively activate spinal interneurons that express the calcium-binding protein calretinin (CR). We show that these interneurons form an interconnected network that can initiate and sustain enhanced excitatory signaling, and directly relay signals to lamina I projection neurons. Photoactivation of CR interneurons in vivo resulted in a significant nocifensive behavior that was morphine sensitive, caused a conditioned place aversion, and was enhanced by spared nerve injury. Furthermore, halorhodopsin-mediated inhibition of these interneurons elevated sensory thresholds. Our results suggest that dorsal horn circuits that involve excitatory CR neurons are important for the generation and amplification of pain and identify these interneurons as a future analgesic target. |
| first_indexed | 2024-04-11T09:13:16Z |
| format | Article |
| id | doaj.art-e0cd9725113d49e9aa0bf5e1f78d7155 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:13:16Z |
| publishDate | 2019-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e0cd9725113d49e9aa0bf5e1f78d71552022-12-22T04:32:28ZengeLife Sciences Publications LtdeLife2050-084X2019-11-01810.7554/eLife.49190Calretinin positive neurons form an excitatory amplifier network in the spinal cord dorsal hornKelly M Smith0https://orcid.org/0000-0002-3039-5002Tyler J Browne1Olivia C Davis2https://orcid.org/0000-0001-8792-7324A Coyle3Kieran A Boyle4Masahiko Watanabe5https://orcid.org/0000-0001-5037-7138Sally A Dickinson6Jacqueline A Iredale7Mark A Gradwell8Phillip Jobling9Robert J Callister10Christopher V Dayas11David I Hughes12https://orcid.org/0000-0003-1260-3362Brett A Graham13https://orcid.org/0000-0002-8070-0503School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, Australia; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, United States; Department of Neurobiology, University of Pittsburgh, Pittsburgh, United StatesSchool of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, AustraliaInstitute of Neuroscience Psychology, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United KingdomInstitute of Neuroscience Psychology, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United KingdomInstitute of Neuroscience Psychology, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United KingdomDepartment of Anatomy, Hokkaido University School of Medicine, Sapporo, JapanSchool of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, AustraliaSchool of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, AustraliaSchool of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, AustraliaSchool of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, AustraliaSchool of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, AustraliaSchool of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, AustraliaInstitute of Neuroscience Psychology, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United KingdomSchool of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute (HMRI), New Lambton Heights, AustraliaNociceptive information is relayed through the spinal cord dorsal horn, a critical area in sensory processing. The neuronal circuits in this region that underpin sensory perception must be clarified to better understand how dysfunction can lead to pathological pain. This study used an optogenetic approach to selectively activate spinal interneurons that express the calcium-binding protein calretinin (CR). We show that these interneurons form an interconnected network that can initiate and sustain enhanced excitatory signaling, and directly relay signals to lamina I projection neurons. Photoactivation of CR interneurons in vivo resulted in a significant nocifensive behavior that was morphine sensitive, caused a conditioned place aversion, and was enhanced by spared nerve injury. Furthermore, halorhodopsin-mediated inhibition of these interneurons elevated sensory thresholds. Our results suggest that dorsal horn circuits that involve excitatory CR neurons are important for the generation and amplification of pain and identify these interneurons as a future analgesic target.https://elifesciences.org/articles/49190painoptogeneticsspinal cordpatch clampinterneuronprojection neurons |
| spellingShingle | Kelly M Smith Tyler J Browne Olivia C Davis A Coyle Kieran A Boyle Masahiko Watanabe Sally A Dickinson Jacqueline A Iredale Mark A Gradwell Phillip Jobling Robert J Callister Christopher V Dayas David I Hughes Brett A Graham Calretinin positive neurons form an excitatory amplifier network in the spinal cord dorsal horn eLife pain optogenetics spinal cord patch clamp interneuron projection neurons |
| title | Calretinin positive neurons form an excitatory amplifier network in the spinal cord dorsal horn |
| title_full | Calretinin positive neurons form an excitatory amplifier network in the spinal cord dorsal horn |
| title_fullStr | Calretinin positive neurons form an excitatory amplifier network in the spinal cord dorsal horn |
| title_full_unstemmed | Calretinin positive neurons form an excitatory amplifier network in the spinal cord dorsal horn |
| title_short | Calretinin positive neurons form an excitatory amplifier network in the spinal cord dorsal horn |
| title_sort | calretinin positive neurons form an excitatory amplifier network in the spinal cord dorsal horn |
| topic | pain optogenetics spinal cord patch clamp interneuron projection neurons |
| url | https://elifesciences.org/articles/49190 |
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