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01-01-2016 | Original Article

Cannabinoid CB1 receptor signaling dichotomously modulates inhibitory and excitatory synaptic transmission in rat inner retina

Authors: Xiao-Han Wang, Yi Wu, Xiao-Fang Yang, Yanying Miao, Chuan-Qiang Zhang, Ling-Dan Dong, Xiong-Li Yang, Zhongfeng Wang

Published in: Brain Structure and Function | Issue 1/2016

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 GABA_A 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 Ca²⁺ channels no matter whether AMPA receptors were blocked. In contrast, WIN reduced the mEPSC frequency by suppressing T-type Ca²⁺ channels only when inhibitory inputs to RGCs were present, which could be in part due to less T-type Ca²⁺ 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.

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Title: Cannabinoid CB1 receptor signaling dichotomously modulates inhibitory and excitatory synaptic transmission in rat inner retina
Authors: Xiao-Han Wang
Yi Wu
Xiao-Fang Yang
Yanying Miao
Chuan-Qiang Zhang
Ling-Dan Dong
Xiong-Li Yang
Zhongfeng Wang
Publication date: 01-01-2016
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 1/2016
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-014-0908-4

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Cannabinoid CB1 receptor signaling dichotomously modulates inhibitory and excitatory synaptic transmission in rat inner retina

Abstract

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Abstract

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