First Author | Cleymaet AM | Year | 2019 |
Journal | Neuroscience | Volume | 408 |
Pages | 400-417 | PubMed ID | 30981862 |
Mgi Jnum | J:283361 | Mgi Id | MGI:6384313 |
Doi | 10.1016/j.neuroscience.2019.04.005 | Citation | Cleymaet AM, et al. (2019) mu-Opioid Receptor Activation Directly Modulates Intrinsically Photosensitive Retinal Ganglion Cells. Neuroscience 408:400-417 |
abstractText | 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 mu-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<40nM), 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. |