...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Retrograde endocannabinoid signaling at striatal synapses requires a regulated postsynaptic release step
【24h】

Retrograde endocannabinoid signaling at striatal synapses requires a regulated postsynaptic release step

机译：纹状体突触的逆行内源性大麻素信号传导需要突触后释放的调控

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Endocannabinoids (eCBs) mediate short- and long-term depression of synaptic strength by retrograde transsynaptic signaling. Previous studies have suggested that an eCB mobilization or release step in the postsynaptic neuron is involved in this retrograde signaling. However, it is not known whether this release process occurs automatically upon eCB synthesis or whether it is regulated by other synaptic factors. To address this issue, we loaded postsynaptic striatal medium spiny neurons (MSNs) with the eCBs anan-damide (AEA) or 2-arachidonoylglycerol and determined the conditions necessary for presynaptic inhibition. We found that presynaptic depression of glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs) induced by postsynaptic eCB loading required a certain level of afferent activation that varied between the different synaptic types. Synaptic depression at excitatory synapses was temperature-dependent and blocked by the eCB membrane transport blockers, VDM11 and UCM707, but did not require activation of metabotropic glutamate receptors, L-calcium channels, nitric oxide, voltage-activated Na~+ channels, or intracellular calcium. Application of the CB,R antagonist, AM251, after depression was established, reversed the decrease in EPSC, but not in IPSC, amplitude. Direct activation of the CB_1 receptor by WIN 55,212-2 initiated synaptic depression that was independent of afferent stimulation. These findings indicate that retrograde eCB signaling requires a postsynaptic release step involving a transporter or carrier that is activated by afferent stimulation/synaptic activation.
机译：内源性大麻素（eCBs）通过逆行的突触传递信号介导突触强度的短期和长期下降。先前的研究表明，突触后神经元中的eCB动员或释放步骤与这种逆行信号有关。但是，尚不知道此释放过程是在eCB合成后自动发生还是由其他突触因子调控。为了解决此问题，我们在突触后纹状体中棘神经元（MSN）中加载了eCBs anan-damide（AEA）或2-arachidonoylglycerol，并确定了突触前抑制的必要条件。我们发现，由突触后eCB加载引起的谷氨酸能兴奋性突触后突触电流（EPSC）和GABA能抑制性突触后突触电流（IPSC）的突触前抑制需要一定水平的传入激活，这种激活在不同突触类型之间有所不同。兴奋性突触中的突触抑制与温度有关，并被eCB膜转运阻滞剂VDM11和UCM707阻滞，但不需要激活代谢型谷氨酸受体，L-钙通道，一氧化氮，电压激活的Na〜+通道或细胞内钙。建立抑郁症后，应用CB，R拮抗剂AM251可以逆转EPSC的下降幅度，但不能抵消IPSC的幅度下降。 WIN 55,212-2对CB_1受体的直接激活引发了突触抑制，该突触抑制与传入刺激无关。这些发现表明，逆行eCB信号传导需要突触后释放步骤，该步骤涉及通过传入刺激/突触激活而激活的转运蛋白或载体。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号