Cannabinoid CB1 receptor signaling dichotomously modulates inhibitory and excitatory synaptic transmission in rat inner retina
Cannabinoid CB1 receptor signaling dichotomously modulates inhibitory and excitatory synaptic transmission in rat inner retina
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DOI：
10.1007/s00429-014-0908-4
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发表时间：
2014
影响因子：
3.1
通讯作者：
Xiao-Han Wang;Yi Wu;Xiao-fang Yang;Y. Miao;Chuan-Qiang Zhang;Ling-Dan Dong;Xiong-Li Yang;Zhongfeng Wang
中科院分区：
文献类型：
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作者：
Xiao-Han Wang;Yi Wu;Xiao-fang Yang;Y. Miao;Chuan-Qiang Zhang;Ling-Dan Dong;Xiong-Li Yang;Zhongfeng Wang
在视网膜内层，神经节细胞（RGCs）整合和处理来自双极细胞（BC）的兴奋性信号和来自无长突细胞（AC）的抑制性信号。采用免疫组化多重标记技术，首次揭示了大麻素CB 1受体（CB 1 R）在大鼠视网膜AC和BCs终末的表达。通过膜片钳技术，我们然后显示了如何激活该受体二分调节的微型抑制性突触后电流（mIPSC），由GABA受体和甘氨酸受体介导，和微型兴奋性突触后电流（mEPSC），由AMPA受体介导，大鼠视网膜切片的RGCs。CB 1 R激动剂WIN 55212 -2（WIN）无论AMPA受体是否被阻断，均可通过抑制L-型Ca ~（2+）通道而降低mIPSC频率。与此相反，WIN通过抑制T型Ca 2+通道降低mEPSC频率只有当抑制性输入的RGCs存在，这可能是部分由于较少的T型Ca 2+通道的锥BCs，突触前的RGCs，在这种条件下处于失活状态。CB 1 R介导的逆行调节的这一独特特征为调节内层视网膜中的兴奋性突触传递提供了一种新的机制。此外，RGCs的去极化抑制了这些细胞的mIPSC，CB 1 R拮抗剂SR 141716消除了这种作用，表明内源性大麻素确实从RGCs释放。
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 GABAAreceptors 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.