Using Opioid Receptors to Expand the Chemogenetic and Optogenetic Toolbox
| Autor: | Paul J. Kenny, Diane M. Damez-Werno |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Neurons
Behavior Animal medicine.drug_class Neuroscience(all) Receptors Opioid kappa General Neuroscience Receptors Opioid mu Optogenetics Biology Inhibitory postsynaptic potential Article Analgesics Opioid nervous system Opioid Opioid receptor medicine Animals Diterpenes GABAergic Neurons Receptor Neuroscience Signal Transduction medicine.drug |
| Zdroj: | Neuron. 86:853-855 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2015.05.014 |
| Popis: | 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, 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 similar kinetics as 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. |
| Databáze: | OpenAIRE |
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