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模拟星形胶质细胞对皮层上下状态切换的调制。

Modelling the modulation of cortical Up-Down state switching by astrocytes.

机构信息

Inria, Villeurbanne, France.

LIRIS UMR5205, University of Lyon, Villeurbanne, France.

出版信息

PLoS Comput Biol. 2022 Jul 21;18(7):e1010296. doi: 10.1371/journal.pcbi.1010296. eCollection 2022 Jul.

Abstract

Up-Down synchronization in neuronal networks refers to spontaneous switches between periods of high collective firing activity (Up state) and periods of silence (Down state). Recent experimental reports have shown that astrocytes can control the emergence of such Up-Down regimes in neural networks, although the molecular or cellular mechanisms that are involved are still uncertain. Here we propose neural network models made of three populations of cells: excitatory neurons, inhibitory neurons and astrocytes, interconnected by synaptic and gliotransmission events, to explore how astrocytes can control this phenomenon. The presence of astrocytes in the models is indeed observed to promote the emergence of Up-Down regimes with realistic characteristics. Our models show that the difference of signalling timescales between astrocytes and neurons (seconds versus milliseconds) can induce a regime where the frequency of gliotransmission events released by the astrocytes does not synchronize with the Up and Down phases of the neurons, but remains essentially stable. However, these gliotransmission events are found to change the localization of the bifurcations in the parameter space so that with the addition of astrocytes, the network enters a bistability region of the dynamics that corresponds to Up-Down synchronization. Taken together, our work provides a theoretical framework to test scenarios and hypotheses on the modulation of Up-Down dynamics by gliotransmission from astrocytes.

摘要

神经元网络中的上下同步是指在高集体发射活动期(Up 状态)和沉默期(Down 状态)之间自发的转换。最近的实验报告表明,星形胶质细胞可以控制神经网络中出现这种上下状态,但涉及的分子或细胞机制仍不确定。在这里,我们提出了由三个细胞群体组成的神经网络模型:兴奋性神经元、抑制性神经元和星形胶质细胞,通过突触和神经胶质传递事件相互连接,以探索星形胶质细胞如何控制这种现象。模型中星形胶质细胞的存在确实被观察到促进了具有现实特征的上下状态的出现。我们的模型表明,星形胶质细胞和神经元之间信号传递时间尺度的差异(秒与毫秒)可以诱导一种状态,其中星形胶质细胞释放的神经胶质传递事件的频率与神经元的上下相位不同步,但基本保持稳定。然而,这些神经胶质传递事件被发现改变了参数空间中分叉的定位,因此,随着星形胶质细胞的加入,网络进入了对应于上下同步的动力学双稳区域。总之,我们的工作提供了一个理论框架,可以用来测试星形胶质细胞的神经胶质传递对上下动力学调制的情景和假设。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4225/9345492/f3c948145285/pcbi.1010296.g001.jpg

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