title: Cannabinoids modulate spontaneous synaptic activity in retinal ganglion cells.
abstract: The endocannabinoid (ECB) system has been found throughout the central nervous system and modulates cell excitability in various forms of short-term plasticity. ECBs and their receptors have also been localized to all retinal cells, and cannabinoid receptor activation has been shown to alter voltage-dependent conductances in several different retinal cell types, suggesting a possible role for cannabinoids in retinal processing. Their effects on synaptic transmission in the mammalian retina, however, have not been previously investigated. Here, we show that exogenous cannabinoids alter spontaneous synaptic transmission onto retinal ganglion cells (RGCs). Using whole-cell voltage-clamp recordings in whole-mount retinas, we measured spontaneous postsynaptic currents (SPSCs) in RGCs in adult and young (P14-P21) mice. We found that the addition of an exogenous cannabinoid agonist, WIN55212-2 (5 μM), caused a significant reversible reduction in the frequency of SPSCs. This change, however, did not alter the kinetics of the SPSCs, indicating a presynaptic locus of action. Using blockers to isolate inhibitory or excitatory currents, we found that cannabinoids significantly reduced the release probability of both GABA and glutamate, respectively. While the addition of cannabinoids reduced the frequency of both GABAergic and glutamatergic SPSCs in both young and adult mice, we found that the largest effect was on GABA-mediated currents in young mice. These results suggest that the ECB system may potentially be involved in the modulation of signal transmission in the retina. Furthermore, they suggest that it might play a role in the developmental maturation of synaptic circuits, and that exogenous cannabinoids are likely able to disrupt retinal processing and consequently alter vision.
authors: Discipline of Physiology, The University of Sydney, Sydney, New South Wales, Australia.
authors: T P
authors: TP
authors: Middleton
authors: D A
authors: DA
authors: Protti
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D048588:Benzoxazines / Q000494:pharmacology; D001703:Biophysics; D002186:Cannabinoids / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011724:Pyridazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D012160:Retina / Q000166:cytology*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000502:physiology; D013028:Space Perception / Q000502:physiology*
chemical_list: D048588:Benzoxazines; D002186:Cannabinoids; D018690:Excitatory Amino Acid Agonists; D018756:GABA Antagonists; D009025:Morpholines; D009281:Naphthalenes; D011724:Pyridazines; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C049853:gabazine