TY - JOUR
T1 - Spatiotemporal Control of Opioid Signaling and Behavior
AU - Siuda, Edward R.
AU - Copits, Bryan A.
AU - Schmidt, Martin J.
AU - Baird, Madison A.
AU - Al-Hasani, Ream
AU - Planer, William J.
AU - Funderburk, Samuel C.
AU - McCall, Jordan G.
AU - Gereau, Robert W.
AU - Bruchas, Michael R.
N1 - Funding Information:
This work is supported by EUREKA NIDA R01DA037152 (to M.R.B.), NIMH F31MH101956 (J.G.M.), Transformative Research Award NS081707 (to R.W.G. and M.R.B.), NIDA K99DA038725 (to R.A.), the W.M. Keck Fellowship in Molecular Medicine (M.J.S. and B.A.C.), and TR32 GM108539 (B.A.C.). M.A.B. was supported by the Howard Hughes Medical Institute. We would like to thank Vijay Samineni and Clint Morgan in the Gereau lab for their assistance. We would also like to thank the Hope Center Viral Core at Washington University-St. Louis. We thank Skylar Spangler, Lamley Lawson, and other members of the Bruchas laboratory for their help revising the manuscript and technical support. We also thank the laboratory of Dr. Evan Kharasch for their technical support.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/5/20
Y1 - 2015/5/20
N2 - Optogenetics is now a widely accepted tool for spatiotemporal manipulation of neuronal activity. However, a majority of optogenetic approaches usebinary 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 invivo 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.
AB - Optogenetics is now a widely accepted tool for spatiotemporal manipulation of neuronal activity. However, a majority of optogenetic approaches usebinary 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 invivo 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.
UR - http://www.scopus.com/inward/record.url?scp=84930238620&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2015.03.066
DO - 10.1016/j.neuron.2015.03.066
M3 - Article
C2 - 25937173
AN - SCOPUS:84930238620
SN - 0896-6273
VL - 86
SP - 923
EP - 935
JO - Neuron
JF - Neuron
IS - 4
ER -