A computational model to investigate astrocytic glutamate uptake influence on synaptic transmission and neuronal spiking
A computational model to investigate astrocytic glutamate uptake influence on synaptic transmission and neuronal spiking
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DOI：
10.3389/fncom.2012.00070
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发表时间：
2012-10-01
影响因子：
3.2
通讯作者：
Berger, Theodore W.
中科院分区：
文献类型：
--
作者：
Allam, Sushmita L.;Ghaderi, Viviane S.;Berger, Theodore W.
在过去的几十年中，我们对星形胶质细胞的看法已从被动支持细胞转变为大脑中的主动处理元素。当前的观点是，星形胶质细胞塑造神经元通信，并且在许多神经退行性疾病中也起着重要作用。尽管人们对星形胶质细胞的重要性的认识越来越大，但神经元 - 尘科细胞通信的确切机制以及星形胶质细胞 - 神经元相互作用的生理后果仍然在很大程度上不清楚。在这项工作中，我们定义了一个建模框架，该框架将允许解决有关星形胶质细胞作用的未解决问题。我们的详细谷氨酸能突触的计算模型促进了神经系统对各种刺激和条件的反应的分析，这些刺激和条件否则很难在实验上获得，尤其是在亚细胞水平上的读数。在本文中，我们扩展了一个详细的谷氨酸能突触模型，以包括星形胶质谷氨酸转运蛋白。我们演示了这些神经胶质转运蛋白如何负责大多数谷氨酸摄取，调节由谷氨酸能突触的离子型AMPA和NMDA受体介导的突触传播。此外，我们研究了这些在突触水平上的局部信号传导如何转化为不同的神经元射击时空模式。配对的脉冲刺激结果表明，当输入间间隔足够长以使受体从脱敏恢复时，星形细胞谷氨酸摄取的效果更为明显。这些结果表明，星形胶质细胞在峰值时间依赖性过程中的重要功能作用，并要求对某些与星形胶质细胞谷氨酸摄取的改变（例如癫痫病）的变化有关的某些神经系统疾病的分子基础进行进一步研究。
Over the past decades, our view of astrocytes has switched from passive support cells to active processing elements in the brain. The current view is that astrocytes shape neuronal communication and also play an important role in many neurodegenerative diseases. Despite the growing awareness of the importance of astrocytes, the exact mechanisms underlying neuron-astrocyte communication and the physiological consequences of astrocytic-neuronal interactions remain largely unclear. In this work, we define a modeling framework that will permit to address unanswered questions regarding the role of astrocytes. Our computational model of a detailed glutamatergic synapse facilitates the analysis of neural system responses to various stimuli and conditions that are otherwise difficult to obtain experimentally, in particular the readouts at the sub-cellular level. In this paper, we extend a detailed glutamatergic synaptic model, to include astrocytic glutamate transporters. We demonstrate how these glial transporters, responsible for the majority of glutamate uptake, modulate synaptic transmission mediated by ionotropic AMPA and NMDA receptors at glutamatergic synapses. Furthermore, we investigate how these local signaling effects at the synaptic level are translated into varying spatio-temporal patterns of neuron firing. Paired pulse stimulation results reveal that the effect of astrocytic glutamate uptake is more apparent when the input inter-spike interval is sufficiently long to allow the receptors to recover from desensitization. These results suggest an important functional role of astrocytes in spike timing dependent processes and demand further investigation of the molecular basis of certain neurological diseases specifically related to alterations in astrocytic glutamate uptake, such as epilepsy.