Howard Hughes Medical Institute, Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California, United States of America.
PLoS Comput Biol. 2013;9(1):e1002856. doi: 10.1371/journal.pcbi.1002856. Epub 2013 Jan 24.
Traumatic brain injury often leads to epileptic seizures. Among other factors, homeostatic synaptic plasticity (HSP) mediates posttraumatic epileptogenesis through unbalanced synaptic scaling, partially compensating for the trauma-incurred loss of neural excitability. HSP is mediated in part by tumor necrosis factor alpha (TNFα), which is released locally from reactive astrocytes early after trauma in response to chronic neuronal inactivity. During this early period, TNFα is likely to be constrained to its glial sources; however, the contribution of glia-mediated spatially localized HSP to post-traumatic epileptogenesis remains poorly understood. We used computational model to investigate the reorganization of collective neural activity early after trauma. Trauma and synaptic scaling transformed asynchronous spiking into paroxysmal discharges. The rate of paroxysms could be reduced by functional segregation of synaptic input into astrocytic microdomains. Thus, we propose that trauma-triggered reactive gliosis could exert both beneficial and deleterious effects on neural activity.
创伤性脑损伤常导致癫痫发作。在其他因素中，通过不平衡的突触缩放，维持性突触可塑性（HSP）介导创伤后癫痫发生，部分补偿了因神经兴奋性丧失而导致的损伤。HSP 部分由肿瘤坏死因子-α（TNFα）介导，TNFα 是创伤后早期反应性星形胶质细胞局部释放的，以应对慢性神经元失活。在此早期阶段，TNFα 可能被限制在其神经胶质来源中；然而，星形胶质细胞介导的局部 HSP 对创伤后癫痫发生的贡献仍知之甚少。我们使用计算模型研究了创伤后早期集体神经活动的重组。创伤和突触缩放将异步尖峰转换为阵发性放电。通过将突触输入功能分离到星形胶质细胞微域中，可以降低阵发性的频率。因此，我们提出创伤触发的反应性神经胶质增生可能对神经活动产生有益和有害的影响。
