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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Order-dependent coincidence detection in cerebellar Purkinje neurons at the inositol trisphosphate receptor.
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Order-dependent coincidence detection in cerebellar Purkinje neurons at the inositol trisphosphate receptor.

机译：小脑浦肯野神经元肌醇三磷酸受体的顺序依赖巧合检测。

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摘要

Associative long-term depression (LTD) at cerebellar parallel fiber-Purkinje cell synapses is sensitive to the temporal order in which the parallel fiber is coactivated with the climbing fiber input, but how order sensitivity is achieved is unknown. Here we show that the cerebellar inositol-1,4,5-trisphosphate (IP3) receptor, whose activation is required for LTD induction, is sensitive in situ to the order of presentation of its coagonists, IP3 and cytoplasmic calcium. By focally photolyzing a novel caged IP3 compound in dendritic spines, we find that pairing IP3 with climbing fiber-mediated calcium entry leads to a large calcium release transient if the climbing fiber is activated up to 100 ms before or up to 500 ms after IP3 uncaging. This asymmetric timing window for coactivation follows the kinetics of calcium removal and IP3 unbinding from the receptor and is not limited by IP3 metabolism. IP3 receptor binding thus acts as an eligibility trace that can drive temporal order-dependent calcium release and LTD induction in Purkinje cells and event order-dependent sensory plasticity in the whole animal.
机译：小脑平行纤维-Purkinje细胞突触的联合长期抑制（LTD）对平行纤维与攀爬纤维输入共同激活的时间顺序敏感，但是如何获得顺序敏感性尚不清楚。在这里，我们显示小脑肌醇-1,4,5-三磷酸（IP3）受体的激活是LTD诱导所必需的，对它的激动剂IP3和胞质钙的呈递顺序是原位敏感的。通过聚焦光解树突棘中的新型笼状IP3化合物，我们发现，如果IP3解封前100 ms或之后500 ms后激活攀岩纤维，则将IP3与攀岩纤维介导的钙进入配对会导致大量的钙释放瞬变。 。共激活的这种不对称时间窗遵循钙去除和IP3从受体释放的动力学，不受IP3代谢的限制。因此，IP3受体结合可作为合格的踪迹，可驱动Purkinje细胞中的时间顺序依赖性钙释放和LTD诱导，以及整个动物中事件顺序依赖性的感觉可塑性。

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