Nonsynaptic NMDA receptors mediate activity-dependent plasticity of gap junctional coupling in the AII amacrine cell network.
Nonsynaptic NMDA receptors mediate activity-dependent plasticity of gap junctional coupling in the AII amacrine cell network.
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DOI：
10.1523/jneurosci.5087-11.2012
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发表时间：
2012-05-16
期刊：
影响因子：
--
通讯作者：
O'Brien J
中科院分区：
文献类型：
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作者：
Kothmann WW;Trexler EB;Whitaker CM;Li W;Massey SC;O'Brien J
许多神经元通过电突触连接成具有突发性的网络。在视网膜中，这些网络中的耦合受到背景照明变化的动态调节，优化了视觉环境的信号整合。然而，人们对这种可塑性的控制机制知之甚少。我们在兔AII无长突细胞中研究了这些机制，AII无长突细胞是一种多功能视网膜神经元，通过Cx36缝隙连接形成电子耦合网络。我们发现双极细胞上的谷氨酸能突触前活动促使Cx36的磷酸化增加，这表明AII网络中的偶联增加。这种磷酸化依赖于与Cx36共存的非突触NMDA受体在AII无长突细胞上的激活，并由CaMKII介导。这种活性依赖的Cx36磷酸化增加与多巴胺驱动的磷酸化减少相反，建立了一种局部动态调节机制，并解释了背景光照对AII偶联的非线性控制。
Many neurons are coupled by electrical synapses into networks that have emergent properties. In the retina, coupling in these networks is dynamically regulated by changes in background illumination, optimizing signal integration for the visual environment. However, the mechanisms that control this plasticity are poorly understood. We have investigated these mechanisms in the rabbit AII amacrine cell, a multifunctional retinal neuron that forms an electrically coupled network via Cx36 gap junctions. We find that presynaptic activity of glutamatergic ON bipolar cells drives increased phosphorylation of Cx36, indicative of increased coupling in the AII network. The phosphorylation is dependent on activation of nonsynaptic NMDA receptors that colocalize with Cx36 on AII amacrine cells, and is mediated by CaMKII. This activity-dependent increase in Cx36 phosphorylation works in opposition to dopamine-driven reduction of phosphorylation, establishing a local dynamic regulatory mechanism, and accounting for the non-linear control of AII coupling by background illumination.