RT Journal Article
SR Electronic
T1 Engagement of spinal- vs prefrontal-projecting locus coeruleus neurons parses analgesia from aversion & anxiety in rats
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 156307
DO 10.1101/156307
A1 Hirschberg, Stefan
A1 Li, Yong
A1 Randall, Andrew
A1 Kremer, Eric J
A1 Pickering, Anthony E
YR 2017
UL http://biorxiv.org/content/early/2017/06/27/156307.abstract
AB The locus coeruleus (LC) projects throughout the brain and spinal cord and is the major source of central noradrenaline. It remains unclear whether the LC acts functionally as a single global effector or as discrete modules. Specifically, while spinal-projections from LC neurons can exert analgesic actions, it is not known whether they can act independently of ascending LC projections. Using viral vectors taken up at axon terminals, we expressed chemogenetic actuators selectively in LC neurons with spinal (LC:SC) or prefrontal cortex (LC:PFC) projections. Activation of the LC:SC module produced robust, lateralised analgesia while activation of LC:PFC produced aversion. In a neuropathic pain model, LC:SC activation reduced hind-limb sensitization and induced conditioned place preference. By contrast, activation of LC:PFC exacerbated spontaneous pain, produced aversion and increased anxiety-like behaviour. This independent, contrasting modulation of pain-related behaviours mediated by distinct noradrenergic modules provides evidence for a discrete functional organisation of the LC.