Cell-type-specific inhibition of the dendritic plateau potential in striatal spiny projection neurons

Cell-type-specific inhibition of the dendritic plateau potential in striatal spiny projection neurons
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DOI:
10.1073/pnas.1704893114
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发表时间:
2017-09-05
影响因子:
11.1
通讯作者:
Kotaleski, Jeanette Hellgren
Kotaleski, Jeanette Hellgren
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Du, Kai;Wu, Yu-Wei;Kotaleski, Jeanette Hellgren

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纹状体棘投射神经元(SPN)接收来自皮层和丘脑的汇聚兴奋性突触输入。远端树突处空间聚集和时间同步的兴奋性输入的激活可能会触发 SPN 的平台电位。这种超线性突触整合对于树突计算至关重要。然而,平台电位如何与随后的兴奋性和抑制性突触输入相互作用仍然未知。通过结合计算模拟、双光子成像、光遗传学以及谷氨酸和 GABA 的双色解笼,我们证明平台电位可以拓宽整合兴奋性输入的时空窗口并促进尖峰。尖峰的时间窗口可以通过 GABA 能抑制以细胞类型特异性的方式精细地控制。这种对平台电位的微妙抑制控制取决于 GABA 能输入的位置和动力学,并通过 NMDA 受体 Mg2+ 阻断的缓解和重建之间的平衡来实现。这些发现代表了控制 SPN 中时空突触整合的机制。
Striatal spiny projection neurons (SPNs) receive convergent excitatory synaptic inputs from the cortex and thalamus. Activation of spatially clustered and temporally synchronized excitatory inputs at the distal dendrites could trigger plateau potentials in SPNs. Such supralinear synaptic integration is crucial for dendritic computation. However, how plateau potentials interact with subsequent excitatory and inhibitory synaptic inputs remains unknown. By combining computational simulation, two-photon imaging, optogenetics, and dual-color uncaging of glutamate and GABA, we demonstrate that plateau potentials can broaden the spatiotemporal window for integrating excitatory inputs and promote spiking. The temporal window of spiking can be delicately controlled by GABAergic inhibition in a cell-type- specific manner. This subtle inhibitory control of plateau potential depends on the location and kinetics of the GABAergic inputs and is achieved by the balance between relief and reestablishment of NMDA receptor Mg2+ block. These findings represent a mechanism for controlling spatiotemporal synaptic integration in SPNs.