μ-Opioid Receptor Activation Directly Modulates Intrinsically Photosensitive Retinal Ganglion Cells
Intrinsically photosensitive retinal ganglion cells (ipRGCs) encode light intensity and trigger reflexive responses to changes in environmental illumination. In addition to functioning as photoreceptors, ipRGCs are post-synaptic neurons in the inner retina, and there is increasing evidence that thei...
Saved in:
| Published in: | Neuroscience Vol. 408; pp. 400 - 417 |
|---|---|
| Main Authors: | , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
Elsevier Ltd
01-06-2019
|
| Subjects: | |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Intrinsically photosensitive retinal ganglion cells (ipRGCs) encode light intensity and trigger reflexive responses to changes in environmental illumination. In addition to functioning as photoreceptors, ipRGCs are post-synaptic neurons in the inner retina, and there is increasing evidence that their output can be influenced by retinal neuromodulators. Here we show that opioids can modulate light-evoked ipRGC signaling, and we demonstrate that the M1, M2 and M3 types of ipRGCs are immunoreactive for μ-opioid receptors (MORs) in both mouse and rat. In the rat retina, application of the MOR-selective agonist DAMGO attenuated light-evoked firing ipRGCs in a dose-dependent manner (IC50 < 40 nM), and this effect was reversed or prevented by co-application of the MOR-selective antagonists CTOP or CTAP. Recordings from solitary ipRGCs, enzymatically dissociated from retinas obtained from melanopsin-driven fluorescent reporter mice, confirmed that DAMGO exerts its effect directly through MORs expressed by ipRGCs. Reduced ipRGC excitability occurred via modulation of voltage-gated potassium and calcium currents. These findings suggest a potential new role for endogenous opioids in the mammalian retina and identify a novel site of action—MORs on ipRGCs—through which opioids might exert effects on reflexive responses to environmental light.
•In the rodent retina M1-M3 types of intrinsically photosensitive ganglion cells (ipRGCs) express μ-opioid receptors (MORs).•Light-evoked firing of ipRGCs is attenuated by the MOR-specific agonist DAMGO in a dose-dependent manner.•MOR activation reduces ipRGC excitability by modulating IK and reducing the amplitude of non-inactivating ICa.•These findings suggest a potential new role for endogenous opioids in the mammalian retina. |
|---|---|
| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 equal contribution current address: Dept. of Biology, University of Akron, Akron, OH 44325 Author contribution Most experiments were performed at Colorado State University (Fort Collins, CO), except for loose patch single cell recordings of light responses that were done at Brown University (Providence, RI) and the MEA recordings from adult rat retinas that were performed at Ohio State University (Columbus, OH). A.T.H. D.M.B and J.V. designed the experiments. A.M.C., S.K.G., M.Y.L, R.E.T, J.V, P.S. A.T.H., J.M.R. and D.M.B. performed the experiments. A.M.C, S.K.G, J.V and J.M.R. analyzed the data. A.T.H., D.M.B and J.V. were involved in the interpretation of the results. A.M.C, S.K.G. drafted the paper, which was critically revised by all authors. All authors approved the final version of the manuscript. All those who qualify for authorship are listed. |
| ISSN: | 0306-4522 1873-7544 1873-7544 |
| DOI: | 10.1016/j.neuroscience.2019.04.005 |