Epileptogenesis due to glia-mediated synaptic scaling
- 4 November 2008
- journal article
- Published by The Royal Society in Journal of The Royal Society Interface
- Vol. 6 (37), 655-668
- https://doi.org/10.1098/rsif.2008.0387
Abstract
Homeostatic regulation of neuronal activity is fundamental for the stable functioning of the cerebral cortex. One form of homeostatic synaptic scaling has been recently shown to be mediated by glial cells that interact with neurons through the diffusible messenger tumour necrosis factor-α (TNF-α). Interestingly, TNF-α is also used by the immune system as a pro-inflammatory messenger, suggesting potential interactions between immune system signalling and the homeostatic regulation of neuronal activity. We present the first computational model of neuron–glia interaction in TNF-α-mediated synaptic scaling. The model shows how under normal conditions the homeostatic mechanism is effective in balancing network activity. After chronic immune activation or TNF-α overexpression by glia, however, the network develops seizure-like activity patterns. This may explain why under certain conditions brain inflammation increases the risk of seizures. Additionally, the model shows that TNF-α diffusion may be responsible for epileptogenesis after localized brain lesions.Keywords
This publication has 42 references indexed in Scilit:
- Postnatal Inflammation Increases Seizure Susceptibility in Adult RatsJournal of Neuroscience, 2008
- Pathological Effect of Homeostatic Synaptic Scaling on Network Dynamics in Diseases of the CortexJournal of Neuroscience, 2008
- Homeostatic signaling: the positive side of negative feedbackCurrent Opinion in Neurobiology, 2007
- The role of inflammation in CNS injury and diseaseBritish Journal of Pharmacology, 2006
- Simple model neurons with AMPA and NMDA filters: role of synaptic time scalesNeurocomputing, 2005
- Tumor necrosis-factor-alpha (TNF-α) induces rapid insertion of Ca2+-permeable α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA)/kainate (Ca-A/K) channels in a subset of hippocampal pyramidal neuronsExperimental Neurology, 2005
- Simple model of spiking neuronsIEEE Transactions on Neural Networks, 2003
- Control of gap-junctional communication in astrocytic networksTrends in Neurosciences, 1996
- Tumor necrosis factor-α-induced gelatinase B causes delayed opening of the blood-brain barrier: an expanded therapeutic windowBrain Research, 1995
- Murine tumor necrosis factor alpha is transported from blood to brain in the mouseJournal of Neuroimmunology, 1993