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Glia as drivers of abnormal neuronal activity

Nature Neuroscience volume 19, pages 28–33 (2016)Cite this article

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Abstract

Reactive astrocytes have been proposed to become incompetent bystanders in epilepsy as a result of cellular changes rendering them unable to perform important housekeeping functions. Indeed, successful surgical treatment of mesiotemporal lobe epilepsy hinges on the removal of the glial scar. New research now extends the role of astrocytes, suggesting that they may drive the disease process by impairing the inhibitory action of neuronal GABA receptors. Here we discuss studies that include hyperexcitability resulting from impaired supply of astrocytic glutamine for neuronal GABA synthesis, and epilepsy resulting from genetically induced astrogliosis or malignant transformation, both of which render the inhibitory neurotransmitter GABA excitatory. In these examples, glial cells alter the expression or function of neuronal proteins involved in excitability. Although epilepsy has traditionally been thought of as a disease caused by changes in neuronal properties exclusively, these new findings challenge us to consider the contribution of glial cells as drivers of epileptogenesis in acquired epilepsies.

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Figure 1: Astrocytes are active modulators of neuronal activity.

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Acknowledgements

This work was supported by grants from the US National Institutes of Health (RO1NS052634, RO1NS082851, RO1NS036692) and the American Brain Tumor Association.

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  1. Virginia Tech Carilion Research Institute, Glial Biology in Health, Disease, and Cancer Center, Roanoke, Virginia, USA

    Stefanie Robel & Harald Sontheimer

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Correspondence to Harald Sontheimer.

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Robel, S., Sontheimer, H. Glia as drivers of abnormal neuronal activity. Nat Neurosci 19, 28–33 (2016). https://doi.org/10.1038/nn.4184

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