title: Cannabinoid CB1 receptor signaling dichotomously modulates inhibitory and excitatory synaptic transmission in rat inner retina.
abstract: In the inner retina, ganglion cells (RGCs) integrate and process excitatory signal from bipolar cells (BCs) and inhibitory signal from amacrine cells (ACs). Using multiple labeling immunohistochemistry, we first revealed the expression of the cannabinoid CB1 receptor (CB1R) at the terminals of ACs and BCs in rat retina. By patch-clamp techniques, we then showed how the activation of this receptor dichotomously regulated miniature inhibitory postsynaptic currents (mIPSCs), mediated by GABAA receptors and glycine receptors, and miniature excitatory postsynaptic currents (mEPSCs), mediated by AMPA receptors, of RGCs in rat retinal slices. WIN55212-2 (WIN), a CB1R agonist, reduced the mIPSC frequency due to an inhibition of L-type Ca(2+) channels no matter whether AMPA receptors were blocked. In contrast, WIN reduced the mEPSC frequency by suppressing T-type Ca(2+) channels only when inhibitory inputs to RGCs were present, which could be in part due to less T-type Ca(2+) channels of cone BCs, presynaptic to RGCs, being in an inactivation state under such condition. This unique feature of CB1R-mediated retrograde regulation provides a novel mechanism for modulating excitatory synaptic transmission in the inner retina. Moreover, depolarization of RGCs suppressed mIPSCs of these cells, an effect that was eliminated by the CB1R antagonist SR141716, suggesting that endocannabinoid is indeed released from RGCs.
authors.affiliation: Institutes of Brain Science, Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China.
authors.forename: Xiao-Han
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Institutes of Brain Science, Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Institutes of Brain Science, Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Yang
authors.affiliation: Institutes of Brain Science, Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China.
authors.forename: Yanying
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Institutes of Brain Science, Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China.
authors.forename: Chuan-Qiang
authors.initials: CQ
authors.lastname: Zhang
authors.affiliation: Institutes of Brain Science, Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China.
authors.forename: Ling-Dan
authors.initials: LD
authors.lastname: Dong
authors.affiliation: Institutes of Brain Science, Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China.
authors.forename: Xiong-Li
authors.initials: XL
authors.lastname: Yang
authors.affiliation: Institutes of Brain Science, Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China. zfwang@fudan.edu.cn.
authors.forename: Zhongfeng
authors.initials: Z
authors.lastname: Wang
mesh_terms: D025042:Amacrine Cells / Q000378:metabolism*; D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D020747:Calcium Channels, T-Type / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials; D053444:Inhibitory Postsynaptic Potentials; D008297:Male; D055369:Miniature Postsynaptic Potentials; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology*; D018091:Receptors, AMPA / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology; D051245:Retinal Bipolar Cells / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D000077285:Rimonabant; D015398:Signal Transduction
chemical_list: D048588:Benzoxazines; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000077285:Rimonabant
keywords: Calcium channels; Cannabinoid CB1 receptor; Inner retina; Synaptic transmission; mEPSCs; mIPSCs