A Wake-Up Call from the Glia?

Science's STKE  25 Apr 2006:
Vol. 2006, Issue 332, pp. tw138
DOI: 10.1126/stke.3322006tw138

Synaptic scaling, a form of activity-dependent plasticity in which the strength of all of the synapses onto a neuron are adjusted uniformly, is believed to promote neural network stability. Prolonged inactivity leads to an increase in the strength of excitatory synapses, whereas increased activity leads to a decrease. Noting that tumor necrosis factor-α (TNF-α) can increase surface expression of AMPARs (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors), Stellwagen and Malenka investigated its possible role in synaptic scaling. Chronic inhibition of neuronal activity or acute exposure to TNF-α increased surface expression of AMPARs in cultured hippocampal neurons. Moreover, acute exposure to conditioned medium from dissociated hippocampal cell cultures containing chronically inhibited neurons increased surface AMPARs, an effect that was blocked by a soluble form of TNFR1 (sTNFR). Chronic exposure to TNF-α or acute exposure to conditioned medium from chronically inhibited neurons also increased the amplitude of miniature excitatory postsynaptic currents (mEPSCs), effects that were sensitive to sTNFR. Chronic activity blockade also increased mEPSC amplitude in neurons in cultured hippocampal slices. Furthermore, no increase in mEPSC amplitude in response to activity blockade occurred in either dissociated cultures or slice cultures from mice lacking TNF-α. Co-culture experiments mixing neurons and glia from wild-type mice with those from mice lacking TNF-α implicated glial TNF-α in the increase in mEPSC amplitude in response to chronic inactivity, and experiments using conditioned medium from glial cultures suggested that glia may respond to glutamate, which would be released during neuronal activity, leading to suppression of TNF-α release. Thus, the authors propose that glial-derived TNF-α may play a role in synaptic scaling by increasing the strength of excitatory synapses during periods of chronic inactivity.

D. Stellwagen, R. C. Malenka, Synaptic scaling mediated by glial TNF-α. Nature 440, 1054-1059 (2006). [PubMed]