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...

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Bibliographic Details
Published in:	eLife Vol. 8
Main Authors:	Smith, Kelly M, Browne, Tyler J, Davis, Olivia C, Coyle, A, Boyle, Kieran A, Watanabe, Masahiko, Dickinson, Sally A, Iredale, Jacqueline A, Gradwell, Mark A, Jobling, Phillip, Callister, Robert J, Dayas, Christopher V, Hughes, David I, Graham, Brett A
Format:	Journal Article
Language:	English
Published:	England eLife Science Publications, Ltd 12-11-2019 eLife Sciences Publications Ltd eLife Sciences Publications, Ltd
Subjects:	Acute pain Analgesics Analgesics, Opioid - pharmacology Animals Aversion Binding proteins Calbindin 2 - genetics Calbindin 2 - metabolism Calcium-binding protein Calmodulin Calretinin Chronic pain Circuits Disease Models, Animal Dorsal horn Gene Expression Halorhodopsins - genetics Halorhodopsins - metabolism Information processing interneuron Interneurons Interneurons - drug effects Interneurons - metabolism Interneurons - pathology Mice Mice, Transgenic Morphine Morphine - pharmacology Nerve Net - drug effects Nerve Net - metabolism Nerve Net - pathology Neuralgia - drug therapy Neuralgia - genetics Neuralgia - metabolism Neuralgia - physiopathology Neurons Neurons - drug effects Neurons - metabolism Neurons - pathology Neuroscience optogenetics Optogenetics - methods pain Pain management Pain perception Pain Threshold - drug effects patch clamp Patch-Clamp Techniques Photic Stimulation Photoactivation Population projection neurons Protein binding Sensory integration Sensory perception Skin Spinal cord Spinal Cord Dorsal Horn - drug effects Spinal Cord Dorsal Horn - metabolism Spinal Cord Dorsal Horn - pathology Tissue Culture Techniques Transgenes Massachusetts mouse pain patch clamp projection neurons neuroscience optogenetics interneuron spinal cord
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	2050-084X 2050-084X
DOI:	10.7554/eLife.49190