Burst-Dependent Bidirectional Plasticity in the Cerebellum Is Driven by Presynaptic NMDA Receptors
Burst-Dependent Bidirectional Plasticity in the Cerebellum Is Driven by Presynaptic NMDA Receptors
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DOI：
10.1016/j.celrep.2016.03.004
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发表时间：
2016-04-05
期刊：
影响因子：
8.8
通讯作者：
Casado, Mariano
中科院分区：
文献类型：
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作者：
Bouvier, Guy;Higgins, David;Casado, Mariano
大量研究表明，小脑功能与平行纤维和浦肯野细胞之间突触的可塑性有关。具体的输入模式如何决定可塑性的结果，以及这些突触可塑性的生物物理学基础，仍然不清楚。在这里，我们的特点的活动模式，导致突触后表达的LTP在体内和体外实验。与LTD的要求类似，我们发现高频爆发是触发LTP所必需的，并且这种爆发依赖的可塑性依赖于突触前NMDA受体和一氧化氮（NO）信号。我们提供了直接的证据，钙离子通过突触前NMDA受体的平行纤维静脉曲张的亚群。最后，我们开发和实验验证了一个机械可塑性模型的基础上NO和钙信号。该模型再现可塑性的结果，从数据和预测的任意模式的突触输入浦肯野细胞的影响，从而提供了一个统一的描述可塑性。
Numerous studies have shown that cerebellar function is related to the plasticity at the synapses between parallel fibers and Purkinje cells. How specific input patterns determine plasticity outcomes, as well as the biophysics underlying plasticity of these synapses, remain unclear. Here, we characterize the patterns of activity that lead to postsynaptically expressed LTP using both in vivo and in vitro experiments. Similar to the requirements of LTD, we find that high-frequency bursts are necessary to trigger LTP and that this burst-dependent plasticity depends on presynaptic NMDA receptors and nitric oxide (NO) signaling. We provide direct evidence for calcium entry through presynaptic NMDA receptors in a subpopulation of parallel fiber varicosities. Finally, we develop and experimentally verify a mechanistic plasticity model based on NO and calcium signaling. The model reproduces plasticity outcomes from data and predicts the effect of arbitrary patterns of synaptic inputs on Purkinje cells, thereby providing a unified description of plasticity.