Journal
NEURON
Volume 98, Issue 5, Pages 963-+Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2018.04.021
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Funding
- NIH [DA010711, DA012864, DA004443, DP5 OD 02304801]
- Canadian Institutes of Health Research [MOP-89716]
- Swiss National Science Foundation [P2EZP3_152173, P300PA_164712]
- Swiss National Science Foundation (SNF) [P2EZP3_152173, P300PA_164712] Funding Source: Swiss National Science Foundation (SNF)
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Opioid receptors (ORs) precisely modulate behavior when activated by native peptide ligands but distort behaviors to produce pathology when activated by non-peptide drugs. A fundamental question is how drugs differ from peptides in their actions on target neurons. Here, we show that drugs differ in the subcellular location at which they activate ORs. We develop a genetically encoded biosensor that directly detects ligand-induced activation of ORs and uncover a real-time map of the spatiotemporal organization of OR activation in living neurons. Peptide agonists produce a characteristic activation pattern initiated in the plasma membrane and propagating to endosomes after receptor internalization. Drugs produce a different activation pattern by additionally driving OR activation in the somatic Golgi apparatus and Golgi elements extending throughout the dendritic arbor. These results establish an approach to probe the cellular basis of neuromodulation and reveal that drugs distort the spatiotemporal landscape of neuronal OR activation.
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