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Cell Rep. 2019 Aug 6;28(6):1429-1438.e4. doi: 10.1016/j.celrep.2019.07.048.

Recruitment of Spinoparabrachial Neurons by Dorsal Horn Calretinin Neurons.

Author information

1
Department of Physiology and Cell Information Systems Group, McGill University, Montréal, QC H3G 0B1, Canada.
2
Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada; Integrated Program in Neuroscience, McGill University, Montréal, QC H3A 2B2, Canada.
3
Departments of Psychology and Anesthesia, McGill University, Montréal, QC H3A 1B1, Canada.
4
Departments of Psychology and Anesthesia, McGill University, Montréal, QC H3A 1B1, Canada; Alan Edwards Center for Research on Pain, McGill University, Suite 3100, Genome Building, Montréal, QC H3A 0G, Canada.
5
Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada; Integrated Program in Neuroscience, McGill University, Montréal, QC H3A 2B2, Canada; Alan Edwards Center for Research on Pain, McGill University, Suite 3100, Genome Building, Montréal, QC H3A 0G, Canada.
6
Department of Physiology and Cell Information Systems Group, McGill University, Montréal, QC H3G 0B1, Canada; Alan Edwards Center for Research on Pain, McGill University, Suite 3100, Genome Building, Montréal, QC H3A 0G, Canada. Electronic address: reza.sharif@mcgill.ca.

Abstract

The dorsal horn of the spinal cord is the first integration site of somatosensory inputs from the periphery. In the superficial layers of the dorsal horn, nociceptive inputs are processed by a complex network of excitatory and inhibitory interneurons whose function and connectivity remain poorly understood. We examined the role of calretinin-expressing interneurons (CR neurons) in such processing and show that they receive direct inputs from nociceptive fibers and polysynaptic inputs from touch-sensitive Aβ fibers. Their activation by chemogenetic or optogenetic stimulation produces mechanical allodynia and nocifensive responses. Furthermore, they monosynaptically engage spinoparabrachial (SPb) neurons in lamina I, suggesting CR neurons modulate one of the major ascending pain pathways of the dorsal horn. In conclusion, we propose a neuronal pathway in which CR neurons are positioned at the junction between nociceptive and innocuous circuits and directly control SPb neurons in lamina I.

KEYWORDS:

Lmx1b; ascending pain pathway; calretinin; chemogenetic; dorsal horn; optogenetic; pain; path-clamp; projection neuron; spinoparabrachial

PMID:
31390558
DOI:
10.1016/j.celrep.2019.07.048
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