Presynaptic Protein Synthesis Is Required for Long-Term Plasticity of GABA Release.
Presynaptic Protein Synthesis Is Required for Long-Term Plasticity of GABA Release.
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DOI：
10.1016/j.neuron.2016.09.040
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发表时间：
2016-10-19
期刊：
影响因子：
16.2
通讯作者：
Castillo PE
中科院分区：
文献类型：
--
作者：
Younts TJ;Monday HR;Dudok B;Klein ME;Jordan BA;Katona I;Castillo PE
神经递质释放的长期变化对正常的大脑功能至关重要。然而，这些变化背后的分子机制知之甚少。虽然蛋白质合成对于突触后可塑性的巩固至关重要，但蛋白质合成是否以及如何调节成熟哺乳动物大脑中的突触前可塑性仍不清楚。在这里，使用配对的全细胞记录在啮齿动物海马切片，我们报告说，突触前蛋白质的合成是需要长期的，但不是短期的，从1型大麻素受体（CB1）表达轴突的GABA释放的可塑性。这种抑制性传递的长期抑制（iLTD）涉及突触前中间神经元轴突而不是胞体中的帽依赖性蛋白质合成。在iLTD的导入期间需要翻译，但不需要维护。从机制上讲，CB1激活通过mTOR途径增强蛋白质合成。此外，使用超分辨率STORM显微镜，我们发现真核核糖体在CB1表达轴突末端。这些研究结果表明，突触前局部蛋白质合成控制神经递质释放在长期可塑性在成熟的哺乳动物大脑。突触前翻译在成熟哺乳动物大脑长期可塑性中的作用存在争议。Younts等人发现突触前蛋白质合成对于啮齿类动物海马抑制性突触GABA释放的长期可塑性至关重要。
Long-term changes of neurotransmitter release are critical for proper brain function. However, the molecular mechanisms underlying these changes are poorly understood. While protein synthesis is crucial for the consolidation of postsynaptic plasticity, whether and how protein synthesis regulates presynaptic plasticity in the mature mammalian brain remains unclear. Here, using paired whole-cell recordings in rodent hippocampal slices, we report that presynaptic protein synthesis is required for long-term, but not short-term, plasticity of GABA release from type-1 cannabinoid receptor (CB1)-expressing axons. This long-term depression of inhibitory transmission (iLTD) involves cap-dependent protein synthesis in presynaptic interneuron axons but not somata. Translation is required during the induction, but not maintenance, of iLTD. Mechanistically, CB1 activation enhances protein synthesis via the mTOR pathway. Furthermore, using super-resolution STORM microscopy, we revealed eukaryotic ribosomes in CB1-expressing axon terminals. These findings suggest that presynaptic local protein synthesis controls neurotransmitter release during long-term plasticity in the mature mammalian brain. The role of presynaptic translation in long-term plasticity in the mature mammalian brain is controversial. Younts et al. find that presynaptic protein synthesis is essential for long-term plasticity of GABA release at rodent hippocampal inhibitory synapses.