TY - JOUR T1 - Optoactivation of Locus Ceruleus Neurons Evokes Bidirectional Changes in Thermal Nociception in Rats JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4148 LP - 4160 DO - 10.1523/JNEUROSCI.4835-13.2014 VL - 34 IS - 12 AU - Louise Hickey AU - Yong Li AU - Sarah J. Fyson AU - Thomas C. Watson AU - Ray Perrins AU - James Hewinson AU - Anja G. Teschemacher AU - Hidemasa Furue AU - Bridget M. Lumb AU - Anthony E. Pickering Y1 - 2014/03/19 UR - http://www.jneurosci.org/content/34/12/4148.abstract N2 - 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°C ± 1.0, p < 0.0001) or pronociceptive (−4.4°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. ER -