Epileptogenesis due to glia-mediated synaptic scaling

Cristina Savin, Jochen Triesch, Michael Meyer-Hermann

Research output: Contribution to journalArticle

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 proinflammatory 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.

Original languageEnglish (US)
Pages (from-to)655-668
Number of pages14
JournalJournal of the Royal Society Interface
Volume6
Issue number37
DOIs
StatePublished - Aug 6 2009

Fingerprint

Neuroglia
Tumor Necrosis Factor-alpha
Immune system
Neurons
Immune System
Brain
Seizures
Encephalitis
Cerebral Cortex
Thermodynamic properties
Chemical activation

Keywords

  • Epilepsy
  • Homeostasis
  • Neuro-immune interaction
  • Neuron-glia interaction
  • Synaptic scaling

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Bioengineering
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering

Cite this

Epileptogenesis due to glia-mediated synaptic scaling. / Savin, Cristina; Triesch, Jochen; Meyer-Hermann, Michael.

In: Journal of the Royal Society Interface, Vol. 6, No. 37, 06.08.2009, p. 655-668.

Research output: Contribution to journalArticle

Savin, Cristina ; Triesch, Jochen ; Meyer-Hermann, Michael. / Epileptogenesis due to glia-mediated synaptic scaling. In: Journal of the Royal Society Interface. 2009 ; Vol. 6, No. 37. pp. 655-668.
@article{88c4ba3055724276ae1b351cd02f22e2,
title = "Epileptogenesis due to glia-mediated synaptic scaling",
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 proinflammatory 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 = "Epilepsy, Homeostasis, Neuro-immune interaction, Neuron-glia interaction, Synaptic scaling",
author = "Cristina Savin and Jochen Triesch and Michael Meyer-Hermann",
year = "2009",
month = "8",
day = "6",
doi = "10.1098/rsif.2008.0387",
language = "English (US)",
volume = "6",
pages = "655--668",
journal = "Journal of the Royal Society Interface",
issn = "1742-5689",
publisher = "Royal Society of London",
number = "37",

}

TY - JOUR

T1 - Epileptogenesis due to glia-mediated synaptic scaling

AU - Savin, Cristina

AU - Triesch, Jochen

AU - Meyer-Hermann, Michael

PY - 2009/8/6

Y1 - 2009/8/6

N2 - 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 proinflammatory 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.

AB - 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 proinflammatory 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.

KW - Epilepsy

KW - Homeostasis

KW - Neuro-immune interaction

KW - Neuron-glia interaction

KW - Synaptic scaling

UR - http://www.scopus.com/inward/record.url?scp=67651006811&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67651006811&partnerID=8YFLogxK

U2 - 10.1098/rsif.2008.0387

DO - 10.1098/rsif.2008.0387

M3 - Article

VL - 6

SP - 655

EP - 668

JO - Journal of the Royal Society Interface

JF - Journal of the Royal Society Interface

SN - 1742-5689

IS - 37

ER -