Garnier Aurélie, Vidal Alexandre, Benali Habib
Laboratoire d'Imagerie Biomédicale (LIB), Sorbonne Universités, UPMC Univ Paris 06, CNRS, INSERM, Paris, 75013, France.
Laboratoire de Mathématiques et Modélisation d'Évry (LaMME), CNRS UMR 8071, Université d'Évry-Val-d'Essonne, Évry, 91000, France.
J Math Neurosci. 2016 Dec;6(1):10. doi: 10.1186/s13408-016-0042-0. Epub 2016 Dec 21.
Recent experimental evidence on the clustering of glutamate and GABA transporters on astrocytic processes surrounding synaptic terminals pose the question of the functional relevance of the astrocytes in the regulation of neural activity. In this perspective, we introduce a new computational model that embeds recent findings on neuron-astrocyte coupling at the mesoscopic scale intra- and inter-layer local neural circuits. The model consists of a mass model for the neural compartment and an astrocyte compartment which controls dynamics of extracellular glutamate and GABA concentrations. By arguments based on bifurcation theory, we use the model to study the impact of deficiency of astrocytic glutamate and GABA uptakes on neural activity. While deficient astrocytic GABA uptake naturally results in increased neuronal inhibition, which in turn results in a decreased neuronal firing, deficient glutamate uptake by astrocytes may either decrease or increase neuronal firing either transiently or permanently. Given the relevance of neuronal hyperexcitability (or lack thereof) in the brain pathophysiology, we provide biophysical conditions for the onset identifying different physiologically relevant regimes of operation for astrocytic uptake transporters.
最近有关谷氨酸和γ-氨基丁酸（GABA）转运体在突触终末周围星形胶质细胞突起上聚集的实验证据，引发了关于星形胶质细胞在神经活动调节中功能相关性的问题。从这个角度出发，我们引入了一种新的计算模型，该模型嵌入了中尺度层内和层间局部神经回路中神经元-星形胶质细胞耦合的最新研究结果。该模型由神经部分的群体模型和控制细胞外谷氨酸和GABA浓度动态的星形胶质细胞部分组成。通过基于分岔理论的论证，我们使用该模型研究星形胶质细胞对谷氨酸和GABA摄取不足对神经活动的影响。虽然星形胶质细胞对GABA摄取不足自然会导致神经元抑制增加，进而导致神经元放电减少，但星形胶质细胞对谷氨酸摄取不足可能会暂时或永久地减少或增加神经元放电。鉴于神经元过度兴奋（或缺乏）在脑部病理生理学中的相关性，我们提供了生物物理条件，以确定星形胶质细胞摄取转运体不同生理相关操作模式的起始点。
