Presynaptic NMDA receptors facilitate short-term plasticity and BDNF release at hippocampal mossy fiber synapses.
Presynaptic NMDA receptors facilitate short-term plasticity and BDNF release at hippocampal mossy fiber synapses.
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DOI：
10.7554/elife.66612
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发表时间：
2021-06-01
期刊：
影响因子：
7.7
通讯作者：
Castillo PE
中科院分区：
文献类型：
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作者：
Lituma PJ;Kwon HB;Alviña K;Luján R;Castillo PE
神经递质释放是一个高度受控的过程，通过突触可以严格调节神经回路中的信息传递。虽然突触前受体（通常由神经递质激活并由神经调节剂调节）提供了一种强大的方式来微调突触功能，但它们对递质释放的活动依赖性变化的贡献仍然知之甚少。在这里，我们报道了啮齿动物海马苔藓纤维钮扣的突触前NMDA受体（preNMDARs）可以被生理相关的活动模式激活，并选择性地增强苔藓纤维输入到CA3锥体细胞和苔藓细胞的短期突触可塑性，而不是抑制性中间神经元。此外，preNMDARs促进脑源性神经营养因子释放并促进突触前钙升高。综上所述，我们的研究结果表明，通过增加突触前钙，preNMDARs微调苔藓纤维神经传递，并可以控制通常发生在体内的齿状颗粒细胞破裂活动中的信息传递。
Neurotransmitter release is a highly controlled process by which synapses can critically regulate information transfer within neural circuits. While presynaptic receptors – typically activated by neurotransmitters and modulated by neuromodulators – provide a powerful way of fine-tuning synaptic function, their contribution to activity-dependent changes in transmitter release remains poorly understood. Here, we report that presynaptic NMDA receptors (preNMDARs) at mossy fiber boutons in the rodent hippocampus can be activated by physiologically relevant patterns of activity and selectively enhance short-term synaptic plasticity at mossy fiber inputs onto CA3 pyramidal cells and mossy cells, but not onto inhibitory interneurons. Moreover, preNMDARs facilitate brain-derived neurotrophic factor release and contribute to presynaptic calcium rise. Taken together, our results indicate that by increasing presynaptic calcium, preNMDARs fine-tune mossy fiber neurotransmission and can control information transfer during dentate granule cell burst activity that normally occur in vivo.