Departments of Neurobiology and Statistics, University of Chicago, Chicago, Illinois, United States of America.
Grossman Center for Quantitative Biology and Human Behavior, University of Chicago, Chicago, Illinois, United States of America.
PLoS Comput Biol. 2023 Aug 9;19(8):e1011290. doi: 10.1371/journal.pcbi.1011290. eCollection 2023 Aug.
Recent experimental works have implicated astrocytes as a significant cell type underlying several neuronal processes in the mammalian brain, from encoding sensory information to neurological disorders. Despite this progress, it is still unclear how astrocytes are communicating with and driving their neuronal neighbors. While previous computational modeling works have helped propose mechanisms responsible for driving these interactions, they have primarily focused on interactions at the synaptic level, with microscale models of calcium dynamics and neurotransmitter diffusion. Since it is computationally infeasible to include the intricate microscale details in a network-scale model, little computational work has been done to understand how astrocytes may be influencing spiking patterns and synchronization of large networks. We overcome this issue by first developing an "effective" astrocyte that can be easily implemented to already established network frameworks. We do this by showing that the astrocyte proximity to a synapse makes synaptic transmission faster, weaker, and less reliable. Thus, our "effective" astrocytes can be incorporated by considering heterogeneous synaptic time constants, which are parametrized only by the degree of astrocytic proximity at that synapse. We then apply our framework to large networks of exponential integrate-and-fire neurons with various spatial structures. Depending on key parameters, such as the number of synapses ensheathed and the strength of this ensheathment, we show that astrocytes can push the network to a synchronous state and exhibit spatially correlated patterns.
最近的实验工作表明,星形胶质细胞是哺乳动物大脑中几种神经元过程的重要细胞类型,从编码感觉信息到神经紊乱。尽管取得了这一进展,但仍不清楚星形胶质细胞如何与神经元邻居进行通信并驱动它们。虽然以前的计算建模工作有助于提出负责驱动这些相互作用的机制,但它们主要集中在突触水平的相互作用上,涉及钙动力学和神经递质扩散的微观模型。由于在网络规模模型中包含复杂的微观细节在计算上是不可行的,因此很少有计算工作来了解星形胶质细胞如何影响大网络的尖峰模式和同步。我们通过首先开发一种“有效”的星形胶质细胞来克服这个问题,这种星形胶质细胞可以很容易地被实施到已经建立的网络框架中。我们通过证明星形胶质细胞与突触的接近程度使突触传递更快、更弱且更不可靠来实现这一点。因此,我们可以通过考虑异构突触时变常数来整合我们的“有效”星形胶质细胞,这些时变常数仅由该突触处星形胶质细胞的接近程度来参数化。然后,我们将该框架应用于具有各种空间结构的指数积分和放电神经元的大型网络。根据关键参数,例如包裹的突触数量和这种包裹的强度,我们表明星形胶质细胞可以将网络推向同步状态,并表现出空间相关的模式。