- Title
- Calretinin positive neurons form an excitatory amplifier network in the spinal cord dorsal horn
- Creator
- Smith, Kelly M.; Browne, Tyler J.; Callister, Robert J.; Dayas, Christopher V.; Hughes, David I.; Graham, Brett A.; Davis, Olivia C.; Coyle, A; Boyle, Kieran A.; Watanabe, Masahiko; Dickinson, Sally A.; Iredale, Jacueline A.; Gradwell, Mark A.; Jobling, Phillip
- Relation
- National Health and Medical Research Council.631000 http://purl.org/au-research/grants/nhmrc/631000
- Relation
- eLIFE Vol. 8, p. 1-32
- Publisher Link
- http://dx.doi.org/10.7554/eLife.49190
- Publisher
- eLIFE Sciences Publications
- Resource Type
- journal article
- Date
- 2019
- 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.
- Subject
- research article; neuroscience; pain; optogenetics; spinal cord; patch clamp; interneuron; projection neurons
- Identifier
- http://hdl.handle.net/1959.13/1456918
- Identifier
- uon:45274
- Identifier
- ISSN:2050-084X
- Rights
- © 2019, Smith et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
- Language
- eng
- Full Text
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