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Endocannabinoid signaling modulates synaptic transmission in the rat inner retina

Endocannabinoid signaling modulates synaptic transmission in...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Xiao-Han WANG~#,Yi WU~#,Yan-Ying MIAO,Xiao-Fang YANG,Zhong-Feng WANG~* Institutes of Brain Science,Institute of Neurobiology and State Key Laboratory of Medical Neurobiology,Fudan University,Shanghai 200032,China

＜正＞Cannabinoid signaling system plays an important role in regulation of many neuronal functions in the CNS. Endocannabinoids function as a retrograde signaling to regulate the synaptic plasticity via activating presynaptic CB1 receptors in many brain areas.To date,the effects of this signaling on synaptic transmission in retina are poorly understood.In the present study,we aimed to explore the modulation of cannabinoid signaling on glycinergic and GABAergic inhibitory inputs,and glutamatergic excitatory inputs to retinal ganglion cells（RGCs）by patch-clamp techniques in rat retinal slices.Our results show that activation of presynaptic CB1 receptors in both GABAergic and glycinergic amacrine cells（ACs）suppressed the frequency of miniature inhibitory postsynaptic currents（mIPSCs）in the RGCs through inhibiting the presynaptic voltage-gated calcium channels.Although the effect of cannabinoid on glutamatergic excitatory inputs from bipolar cells to the RGCs is basically similar,the tonic inhibitory inputs from the ACs to the bipolar cells are necessary.Blocking these inhibitory inputs eliminated completely the suppression effect of cannabinoid on the excitatory inputs to the RGCs.The underlying mechanism is that deinhibition-induced depolarization of bipolar cells inactivates the presynaptic T-type calcium channels that is a target of the activated presynaptic CB1 receptors in the bipolar cells.Our data revealed a new mechanism of cannabinoid modulating synaptic transmission in the inner retina.

关键词： cannabinoid CBl receptor inner retina mlPSCs mEPSCs deinhibition

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

Cannabinoid CB1 receptor signaling dichotomously modulates e...

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中国神经科学学会第十届全国学术会议

作者： Xiao-Han Wang Yi Wu Xiao-Fang Yang Yanying Miao Ling-Dan Dong Xiong-Li Yang Zhongfeng Wang Institutes of Brain Science Institute of Neurobiology and State Key Laboratory of Medical NeurobiologyFudan University

In the inner retina,a neuronal circuit formed by ganglion cells（RGCs）,amacrine cells（ACs） and bipolar cells（BCs） integrates and modulates visual information.We investigated how activation of the cannabinoid CB1receptor（CB1R）,expressed on the terminals of ACs and BCs,as demonstrated by multiple labeling immunohistochemistry,regulates mTPSCs and mEPSCs of RGCs in rat retina.WIN55121-2（WIN）,a CB1R agonist,suppressed mTPSCs of RGCs by inhibiting L-type calcium channels of ACs.In contrast,the existence of inhibitory inputs from ACs to BCs was indispensable for WTN-induced suppression of mEPSCs of RGCs.Furthermore,the depolarized membrane potential of BCs in the absence of inhibitory inputs from ACs inactivated the T-type calcium channel that was responsible for the generation of RGC mEPSCs,so mat this channel could not be regulated.When the inactivation was eliminated by the hyperpolarization caused by the inhibitory inputs,the T-type channel was inhibited by activation of presynaptic CBlRs on BCs,which resulted in the suppression of the mEPSCs.This unique feature of CB lR-mediated retrograde regulation provides a novel mechanism for modulating excitatory synaptic transmission in the inner retina.

关键词： cannabinoid CB1 receptor inner retina synaptic transmission mEPSCs mIPSCs T-type calcium channel retinal ganglion cell

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