Glutamate-Bound NMDARs Arising from In Vivo-like Network Activity Extend Spatio-temporal Integration in a L5 Cortical Pyramidal Cell Model
Glutamate-Bound NMDARs Arising from In Vivo-like Network Activity Extend Spatio-temporal Integration in a L5 Cortical Pyramidal Cell Model
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DOI：
10.1371/journal.pcbi.1003590
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发表时间：
2014-04-01
影响因子：
4.3
通讯作者：
Silver, R. Angus
中科院分区：
文献类型：
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作者：
Farinella, Matteo;Ruedt, Daniel T.;Silver, R. Angus
在体内，皮层锥体细胞受到持续网络活动引起的异步突触输入的轰击。然而，人们对这种背景突触输入如何与非线性树突机制相互作用知之甚少。我们修改了现有的第5层（L5）锥体细胞模型，以探索在体内观察到的网络活性水平如何改变顶端树突丛中的树突整合。本研究表明，异步背景兴奋性输入增加了神经元增益，并将刺激诱发的突触输入的时间和空间整合扩展到树突丛。快速和缓慢抑制性突触传导的添加，具有与树突靶向中间神经元相似的特性，提供了平衡的“背景配置”，部分抵消了这些影响，表明抑制可以调节簇中的时空整合。兴奋性背景输入降低了NMDA受体介导的树突尖峰的阈值，延长了它们的持续时间，并增加了邻近分支发生额外再生事件的可能性。这些影响也被观察到在一个被动的模型中，所有的非突触电压门控电导被移除。我们的研究结果表明，由持续的网络活动产生的谷氨酸结合的NMDA受体可以提供强大的空间分布的非线性树突电导。这可能使L5锥体细胞作为局部网络活动的功能改变其整合特性，潜在地允许集群和空间分布的突触输入在延长的时间尺度上整合。
In vivo, cortical pyramidal cells are bombarded by asynchronous synaptic input arising from ongoing network activity. However, little is known about how such background' synaptic input interacts with nonlinear dendritic mechanisms. We have modified an existing model of a layer 5 (L5) pyramidal cell to explore how dendritic integration in the apical dendritic tuft could be altered by the levels of network activity observed in vivo. Here we show that asynchronous background excitatory input increases neuronal gain and extends both temporal and spatial integration of stimulus-evoked synaptic input onto the dendritic tuft. Addition of fast and slow inhibitory synaptic conductances, with properties similar to those from dendritic targeting interneurons, that provided a balanced' background configuration, partially counteracted these effects, suggesting that inhibition can tune spatio-temporal integration in the tuft. Excitatory background input lowered the threshold for NMDA receptor-mediated dendritic spikes, extended their duration and increased the probability of additional regenerative events occurring in neighbouring branches. These effects were also observed in a passive model where all the non-synaptic voltage-gated conductances were removed. Our results show that glutamate-bound NMDA receptors arising from ongoing network activity can provide a powerful spatially distributed nonlinear dendritic conductance. This may enable L5 pyramidal cells to change their integrative properties as a function of local network activity, potentially allowing both clustered and spatially distributed synaptic inputs to be integrated over extended timescales.