星形胶质细胞摄取谷氨酸对V1方向调谐的突触和突触外效应的计算研究
A computational study on synaptic and extrasynaptic effects of astrocyte glutamate uptake on orientation tuning in V1
摘要：
星形胶质细胞通过谷氨酸转运体对突触间隙附近的谷氨酸浓度和细胞外谷氨酸的严格控制来影响神经传递。雪貂和小鼠初级视觉皮层的体内研究支持了它们与信息表征的相关性。在雪貂阻断谷氨酸转运的神经元扩大调谐曲线，并加强在首选方向的反应。在谷氨酸转运蛋白表达减少的基因敲除小鼠中，观察到了尖锐的调谐。然而，目前还不清楚谷氨酸浓度的焦点和环境变化如何影响刺激表征。在这里，我们开发了一个计算框架，它允许调查的突触和突触外谷氨酸摄取的方向调谐与风车域（雪貂）或盐和胡椒（小鼠）组织的递归连接的网络模型的影响。该模型认为，谷氨酸的摄取影响兴奋性和抑制性神经元对网络活动的贡献时，形状的信息表示。也就是说，加强兴奋性神经元的贡献通常会扩大调谐并提高响应。相反，加强抑制性神经元的贡献可以对调谐产生锐化效应。此外，局部表征拓扑结构也发挥了作用：在风车域模型中，效应在相邻神经元共享首选方向的区域内最强。在风车周围以及盐和胡椒网络中，这种影响不那么强烈。我们的模型提出，药物干预雪貂增加了兴奋细胞的贡献，而在小鼠中的表达减少增加了抑制细胞对网络活动的贡献。
英文摘要：
Astrocytes affect neural transmission by a tight control via glutamate transporters on glutamate concentrations in direct vicinity to the synaptic cleft and by extracellular glutamate. Their relevance for information representation has been supported by in-vivo studies in ferret and mouse primary visual cortex. In ferret blocking glutamate transport pharmacologically broadened tuning curves and enhanced the response at preferred orientation. In knock-out mice with reduced expression of glutamate transporters sharpened tuning was observed. It is however unclear how focal and ambient changes in glutamate concentration affect stimulus representation. Here we develop a computational framework, which allows the investigation of synaptic and extrasynaptic effects of glutamate uptake on orientation tuning in recurrently connected network models with pinwheel-domain (ferret) or salt-and-pepper (mouse) organization. This model proposed that glutamate uptake shapes information representation when it affects the contribution of excitatory and inhibitory neurons to the network activity. Namely, strengthening the contribution of excitatory neurons generally broadens tuning and elevates the response. In contrast, strengthening the contribution of inhibitory neurons can have a sharpening effect on tuning. In addition local representational topology also plays a role: In the pinwheel-domain model effects were strongest within domains - regions where neighboring neurons share preferred orientations. Around pinwheels but also within salt-and-pepper networks the effects were less strong. Our model proposes that the pharmacological intervention in ferret increases the contribution of excitatory cells, while the reduced expression in mouse increases the contribution of inhibitory cells to network activity.
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