Journal
JOURNAL OF NEUROSCIENCE
Volume 34, Issue 12, Pages 4148-4160Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4835-13.2014
Keywords
ChannelRhodopsin2; endogenous analgesia; lentiviral vector; locus ceruleus; noradrenergic; pain
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Funding
- Wellcome Trust
- British Heart Foundation
- Grants-in-Aid for Scientific Research [23390156, 25670289, 24390148] Funding Source: KAKEN
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Pontospinal noradrenergic neurons are thought to form part of a descending endogenous analgesic system that exerts inhibitory influences on spinal nociception. Using optogenetic targeting, we tested the hypothesis that excitation of the locus ceruleus (LC) is antinociceptive. We transduced rat LC neurons by direct injection of a lentiviral vector expressing channelrhodopsin2 under the control of the PRS promoter. Subsequent optoactivation of the LC evoked repeatable, robust, antinociceptive (-4.7 degrees C +/- 1.0, p < 0.0001) or pronociceptive (-4.4 degrees C +/- 0.7, p < 0.0001) changes in hindpaw thermal withdrawal thresholds. Post hoc anatomical characterization of the distribution of transduced somata referenced against the position of the optical fiber and subsequent further functional analysis showed that antinociceptive actions were evoked from a distinct, ventral subpopulation of LC neurons. Therefore, the LC is capable of exerting potent, discrete, bidirectional influences on thermal nociception that are produced by specific subpopulations of noradrenergic neurons. This reflects an underlying functional heterogeneity of the influence of the LC on the processing of nociceptive information.
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