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首页> 外文期刊>Philosophical Transactions of the Royal Society of London, Series B. Biological Sciences >Cannabinoid receptors contribute to astroglial Ca~(2+)-signalling and control of synaptic plasticity in the neocortex
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Cannabinoid receptors contribute to astroglial Ca~(2+)-signalling and control of synaptic plasticity in the neocortex

机译：大麻素受体促进星形胶质细胞Ca〜（2+）信号传导并控制新皮层中的突触可塑性。

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Communication between neuronal and glial cells is thought to be very important for many brain functions. Acting via release of gliotransmitters, astrocytes can modulate synaptic strength. The mechanisms underlying ATP release from astrocytes remain uncertain with exocytosis being the most intriguing and debated pathway. We have demonstrated that ATP and D-serine can be released from cortical astrocytes in situ by a SNARE-complex-dependent mechanism. Exocytosis of ATP from astrocytes can activate post-synaptic P2X receptors in the adjacent neurons, causing a downregulation of synaptic and extrasynaptic GABA receptors in cortical pyramidal neurons. We showed that release of gliotransmitters is important for the NMDA receptordependent synaptic plasticity in the neocortex. Firstly, induction of long-term potentiation (LTP) by five episodes of theta-burst stimulation (TBS) was impaired in the neocortex of dominant-negative (dn)-SNARE mice. The LTP was rescued in the dn-SNARE mice by application of exogenous non-hydrolysable ATP analogues. Secondly, we observed that weak sub-threshold stimulation (two TBS episodes) became able to induce LTP when astrocytes were additionally activated via CB-1 receptors. This facilitationwas dependent on activity of ATP receptors and was abolished in the dn-SNARE mice. Our results strongly support the physiological relevance of glial exocytosis for glia-neuron communications and brain function.
机译：神经元和神经胶质细胞之间的通讯被认为对许多大脑功能非常重要。通过释放神经胶质递质，星形胶质细胞可以调节突触强度。星形胶质细胞释放ATP的基本机制仍然不确定，胞吐作用是最吸引人和争议的途径。我们已经证明ATP和D丝氨酸可以通过SNARE复杂依赖机制从皮质星形胶质细胞原位释放。来自星形胶质细胞的ATP胞吐作用可以激活邻近神经元中的突触后P2X受体，从而导致皮质锥体神经元中突触和突触外GABA受体的下调。我们表明神经胶质递质的释放对于新皮质中NMDA受体依赖性突触可塑性很重要。首先，在显性阴性（dn）-SNARE小鼠的新皮层中，五次Theta-burst刺激（TBS）引起的长期增强（LTP）诱导受到损害。通过应用外源不可水解的ATP类似物，在dn-SNARE小鼠中挽救了LTP。其次，我们观察到当星形胶质细胞还通过CB-1受体额外激活时，弱亚阈值刺激（两次TBS发作）变得能够诱导LTP。这种促进依赖于ATP受体的活性，并在dn-SNARE小鼠中被取消。我们的研究结果强烈支持胶质细胞胞吐作用与胶质神经元通讯和脑功能的生理相关性。

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