Long-term potentiation of neuronal glutamate transporters
Long-term potentiation of neuronal glutamate transporters
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DOI：
10.1016/j.neuron.2005.04.033
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发表时间：
2005-06-02
期刊：
影响因子：
16.2
通讯作者：
Linden, DJ
中科院分区：
文献类型：
--
作者：
Shen, Y;Linden, DJ
突触强度的持续性、使用依赖性调节已被证明是谷氨酸介导的快速突触传递的基础，并被假设为从记忆到成瘾的持续性行为变化的基础。在突触处释放的谷氨酸通过神经胶质和突触后神经元中的兴奋性氨基酸转运体（EAAT）的作用被隔离。因此，谷氨酸转运体功能的功效对于调节谷氨酸溢出到相邻的突触前和突触后受体以及随后诱导可塑性或兴奋性毒性过程至关重要。在这里，我们报告，强直刺激小脑攀爬纤维浦肯野细胞突触的结果在长时程增强（LTP）的攀爬纤维诱发的谷氨酸转运体电流记录在浦肯野细胞。这种LTP在突触后表达，需要mGluR 1/PKC级联反应的激活。连同同时诱导的突触后AMPA受体的长期抑制（LTD），这可能反映了一个集成的抗兴奋性毒性细胞反应强攀爬纤维突触激活，如缺血发作后发生。
Persistent, use-dependent modulation of synaptic strength has been demonstrated for fast synaptic transmission mediated by glutamate and has been hypothesized to underlie persistent behavioral changes ranging from memory to addiction. Glutamate released at synapses is sequestered by the action of excitatory amino acid transporters (EAATs) in glia and postsynaptic neurons. So, the efficacy of glutamate transporter function is crucial for regulating glutamate spillover to adjacent presynaptic and postsynaptic receptors and the consequent induction of plastic or excitotoxic processes. Here, we report that tetanic stimulation of cerebellar climbing fiber-Purkinje cell synapses results in long-term potentiation (LTP) of a climbing fiber-evoked glutamate transporter current recorded in Purkinje cells. This LTP is postsynaptically expressed and requires activation of an mGluR1/PKC cascade. Together with a simultaneously induced long-term depression (LTD) of postsynaptic AMPA receptors, this might reflect an integrated antiexcitotoxic cellular response to strong climbing fiber synaptic activation, as occurs following an ischemic episode.