Μ-Opioid Receptor Activation Directly Modulates Intrinsically Photosensitive Retinal Ganglion Cells. (1st June 2019)

• Record Type: Journal Article
• Authors: Cleymaet, Allison M.; Gallagher, Shannon K.; Tooker, Ryan E.; Lipin, Mikhail Y.; Renna, Jordan M.; Sodhi, Puneet; Berg, Daniel; Hartwick, Andrew T.E.; Berson, David M.; Vigh, Jozsef
• Is Part Of: Neuroscience. Volume 408(2019)
• Page Start: 400
• Page End: 417
• Publication Date: 2019-06-01
• Subjects: AC adenylate cyclase -- 4-AP 4-Aminopyridine -- BLA basolateral amygdala -- IK(Ca) calcium-dependent potassium currents -- CGP54626 [S-(R*, R*)]-[3-[[1-(3, 4-Dichlorophenyl)ethyl]amino-2-hydroxypropyl], (cyclohexylmethyl) phosphinic acid -- CTOP H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 CTAP, H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 -- DAMGO [D-Ala2, MePhe4, Gly-ol5]-enkephalin -- D-AP5 D-(−)-2-Amino-5-phosphonopentanoic acid -- D-AP7 D-(−)-2-Amino-7-phosphonoheptanoic acid -- EGFP enhanced green fluorescent protein -- GAD glutamic acid decarboxylase -- GCL ganglion cell layer -- GIRK G-protein-activated inwardly rectifying K+ channels -- IC50 half-blocking concentration -- V0.5 half-activation potential -- HEPES 4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid -- INL inner nuclear layer -- IPL inner plexiform layer -- ipRGCs intrinsically photosensitive retinal ganglion cells -- L-AP4 L-(+)-2-Amino-4-phosphonobutyric acid -- LJP liquid junction potential -- Vm membrane potential -- MEA multielectrode array -- MOR μ-opioid receptor -- NBQX 2, 3-Dioxo-6-nitro-1, 2, 3, 4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide -- ONL outer nuclear layer -- OPL outer plexiform layer -- Rs series resistance -- TPMPA (1, 2, 5, 6-Tetrahydropyridin-4-yl) methylphosphinic acid -- TTX tetrodotoxin -- Cav voltage-gated calcium channel -- ICa voltage-gated calcium current -- Kv voltage-gated potassium channel -- IK voltage-gated potassium current -- INa voltage-gated sodium current -- V0.05 command voltage at which the resulting IK was 5% of the peak; opioids -- retina -- intrinsically photosensitive ganglion cell; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2019.04.005
• Languages: English
• ISSNs: 0306-4522

Abstract

Abstract: 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. Highlights: 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.