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Neuron. 2015 May 20;86(4):923-35. doi: 10.1016/j.neuron.2015.03.066. Epub 2015 Apr 30.

Spatiotemporal control of opioid signaling and behavior.

Author information

1
Department of Anesthesiology, Basic Research Division, Washington University in St. Louis, St. Louis, MO 63110, USA; Division of Biological and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
Department of Anesthesiology, Basic Research Division, Washington University in St. Louis, St. Louis, MO 63110, USA; Washington University Pain Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
3
Department of Anesthesiology, Basic Research Division, Washington University in St. Louis, St. Louis, MO 63110, USA.
4
Department of Anesthesiology, Basic Research Division, Washington University in St. Louis, St. Louis, MO 63110, USA; Division of Biological and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA; Washington University Pain Center, Washington University in St. Louis, St. Louis, MO 63110, USA; Department of Anatomy and Neurobiology, Washington University in St. Louis, St. Louis, MO 63110, USA.
5
Department of Anesthesiology, Basic Research Division, Washington University in St. Louis, St. Louis, MO 63110, USA; Division of Biological and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA; Washington University Pain Center, Washington University in St. Louis, St. Louis, MO 63110, USA; Department of Anatomy and Neurobiology, Washington University in St. Louis, St. Louis, MO 63110, USA; Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63110, USA. Electronic address: bruchasm@wustl.edu.

Abstract

Optogenetics is now a widely accepted tool for spatiotemporal manipulation of neuronal activity. However, a majority of optogenetic approaches use binary on/off control schemes. Here, we extend the optogenetic toolset by developing a neuromodulatory approach using a rationale-based design to generate a Gi-coupled, optically sensitive, mu-opioid-like receptor, which we term opto-MOR. We demonstrate that opto-MOR engages canonical mu-opioid signaling through inhibition of adenylyl cyclase, activation of MAPK and G protein-gated inward rectifying potassium (GIRK) channels and internalizes with kinetics similar to that of the mu-opioid receptor. To assess in vivo utility, we expressed a Cre-dependent viral opto-MOR in RMTg/VTA GABAergic neurons, which led to a real-time place preference. In contrast, expression of opto-MOR in GABAergic neurons of the ventral pallidum hedonic cold spot led to real-time place aversion. This tool has generalizable application for spatiotemporal control of opioid signaling and, furthermore, can be used broadly for mimicking endogenous neuronal inhibition pathways.

PMID:
25937173
PMCID:
PMC4441608
DOI:
10.1016/j.neuron.2015.03.066
[Indexed for MEDLINE]
Free PMC Article
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