Burst-Time-Dependent Plasticity Robustly Guides ON/OFF Segregation in the Lateral Geniculate Nucleus
Burst-Time-Dependent Plasticity Robustly Guides ON/OFF Segregation in the Lateral Geniculate Nucleus
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DOI：
10.1371/journal.pcbi.1000618
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发表时间：
2009-12-01
影响因子：
4.3
通讯作者：
Eglen, Stephen J.
中科院分区：
文献类型：
--
作者：
Gjorgjieva, Julijana;Toyoizumi, Taro;Eglen, Stephen J.
自发性视网膜活动（称为“波”）在发育过程中重塑与外侧膝状体核（LGN）的突触连接。用多电极阵列记录的小鼠视网膜波的分析表明，LGN中功能不同（ON和OFF）的视网膜神经节细胞（RGC）的分离的线索可能是它们的放电中的去极化，其中ON细胞先于OFF细胞一秒。使用记录的视网膜波作为输入，与两种不同的建模方法，我们探索基于时间的可塑性规则的突触权重的演变，以确定关键功能的ON/OFF隔离。首先，我们分析推导出一个线性模型的ON和OFF权重的演变，了解突触可塑性规则如何提取输入发射属性，以指导隔离。其次，我们模拟突触后活动的非线性积分和火灾模型与线性模型的结果进行比较。我们发现，尖峰时间依赖的可塑性，修改突触权重的基础上毫秒长的时间和顺序的前和突触后尖峰，未能隔离开和关视网膜输入的情况下，正常化。实施自我平衡机制会导致隔离，但只有在仔细调整参数的情况下。此外，延长尖峰积分时间尺度以匹配第二长输入相关时间尺度总是导致ON隔离，因为ON单元在OFF单元之前激发。我们发现，突发时间依赖的可塑性可以强大地引导开/关隔离在LGN没有正常化，通过整合前和突触后的突发，无论其发射顺序和秒长的时间尺度。我们预测，LGN神经元将成为ON或OFF响应的基础上连接到它的邻近RGCs的发射模式的本地竞争。最后，我们证明了一致性与ON/OFF隔离雪貂，尽管在视网膜波的发射特性的差异。我们的模型表明，视网膜波的不同输入统计数据可以通过基于突发的规则来鲁棒地解释，该规则是不同物种的视网膜小突可塑性的基础。
Spontaneous retinal activity (known as "waves") remodels synaptic connectivity to the lateral geniculate nucleus (LGN) during development. Analysis of retinal waves recorded with multielectrode arrays in mouse suggested that a cue for the segregation of functionally distinct (ON and OFF) retinal ganglion cells (RGCs) in the LGN may be a desynchronization in their firing, where ON cells precede OFF cells by one second. Using the recorded retinal waves as input, with two different modeling approaches we explore timing-based plasticity rules for the evolution of synaptic weights to identify key features underlying ON/OFF segregation. First, we analytically derive a linear model for the evolution of ON and OFF weights, to understand how synaptic plasticity rules extract input firing properties to guide segregation. Second, we simulate postsynaptic activity with a nonlinear integrate-and-fire model to compare findings with the linear model. We find that spike-time-dependent plasticity, which modifies synaptic weights based on millisecond-long timing and order of pre- and postsynaptic spikes, fails to segregate ON and OFF retinal inputs in the absence of normalization. Implementing homeostatic mechanisms results in segregation, but only with carefully-tuned parameters. Furthermore, extending spike integration timescales to match the second-long input correlation timescales always leads to ON segregation because ON cells fire before OFF cells. We show that burst-time-dependent plasticity can robustly guide ON/OFF segregation in the LGN without normalization, by integrating pre- and postsynaptic bursts irrespective of their firing order and over second-long timescales. We predict that an LGN neuron will become ON-or OFF-responsive based on a local competition of the firing patterns of neighboring RGCs connecting to it. Finally, we demonstrate consistency with ON/OFF segregation in ferret, despite differences in the firing properties of retinal waves. Our model suggests that diverse input statistics of retinal waves can be robustly interpreted by a burst-based rule, which underlies retinogeniculate plasticity across different species.