Divide and conquer: functional segregation of synaptic inputs by astrocytic microdomains could alleviate paroxysmal activity following brain trauma.
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.
Howard Hughes Medical Institute, Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California, United States of America. volman@salk.edu
Vladislav
V
Volman
Maxim
M
Bazhenov
Terrence J
TJ
Sejnowski
D001253:Astrocytes / Q000502:physiology*; D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008962:Models, Theoretical; D016202:N-Methylaspartate / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D016202:N-Methylaspartate