The capacity to generate action potentials, prime purview of neurons, is actually not exclusive to those cells, according to new research showing some glia are also capable of spiking electrical activity. In the March 2 issue of Nature Neuroscience online, Ragnhildur Karadottir, David Attwell, and colleagues at University College London present evidence that a subset of oligodendrocyte precursor glia can display action potentials and receive synaptic input. Apparently these same cells are preferentially vulnerable to ischemia-induced glutamate toxicity.
Besides being important to understanding the basic functions of glia, the finding puts a spotlight on white matter, the stuff of the brain made up of myelinated axons plus their associated glia. Degeneration of these white matter tracts is a common finding in Alzheimer disease, although the causes are not clear. The new results raise the possibility that excitotoxicity, or some other processes related to the activity of glia, could play a role in white matter loss.
In the study, Karadottir and colleagues distinguished two subtypes of oligodendrocyte precursor glia cells (OPCs) in postnatal rat CNS white matter. The two kinds of cells look morphologically identical, but whole cell recording experiments revealed that one type showed voltage-gated sodium and potassium currents. The current-generating cells expressed voltage-gated sodium channels, while the electrically silent cells did not. Ultimately, the researchers found that cells expressing the sodium channels generated action potentials upon depolarization.
In adult rats, the two cells types were readily apparent, where 70 percent of OPCs expressed sodium channels. To the authors, the channel expression did not appear to be a function of the developmental stage of the cells or their place in the cell cycle, based on the cells’ morphology and expression of maturation markers.
Axons in white matter can release neurotransmitters onto OPCs (see ARF related news story), and the new study indicates that spiking OPCs have the capacity to respond to that stimulus. Both glutamate- and GABA-induced currents were detected in the sodium channel-expressing cells, while cells without the sodium current rarely showed detectable synaptic input. “Thus, the two classes of OPCs sense their environment in different ways,” the authors write.
Because the spiking glia respond more avidly to glutamate, the authors hypothesized that they might be sensitive to the toxic elevation of that neurotransmitter that occurs in stroke or trauma. When the investigators induced ischemia in brain slices, OPCs with sodium channels experienced larger glutamate-induced currents. One hour later, a third of the cells of the spiking subtype were dead, compared with only 2 percent of the cells lacking the sodium channel. Cell death was blocked by glutamate receptor antagonists, consistent with a mechanism of death by excitotoxicity. The results suggest that spiking glia are preferentially damaged in stroke or injury.
“Our demonstration that white matter glial cells can generate trains of action potentials challenges current concepts of the distinction between neurons and glia,” the authors write. They do not yet understand the role of the glial activity, but as the cells have no known synaptic output mechanism, the scientists speculate that the action potentials could regulate cell activity such as myelination of nearby axons.—Pat McCaffrey
- Káradóttir R, Hamilton NB, Bakiri Y, Attwell D. Spiking and nonspiking classes of oligodendrocyte precursor glia in CNS white matter. Nat Neurosci. 2008 Apr;11(4):450-6. PubMed.