When the energy supply is cut off to part of the brain, as occurs when a blood vessel gets blocked in stroke, bad things happen. With the cells starved of power, the ion gradients across cell membranes run down, leading to a reversal of glutamate transporters, and thus to glutamate release in the grey matter which over-activates NMDA receptors and triggers neuronal death.

Less well known is the fact that neurotransmitter signalling is also a major contributor to mental and physical impairment in white matter diseases like cerebral palsy, spinal cord injury and multiple sclerosis.

In my lecture I will present our recent findings on glutamate signalling to mature oligodendrocytes (relevant to spinal cord injury and multiple sclerosis) and to oligodendrocyte precursor cells (relevant to cerebral palsy). I will show that, contrary to what was previously thought, NMDA receptors can mediate damage to mature oligodendrocytes, and that oligodendrocyte precursor glia form two classes, one of which fires action potentials and dies preferentially as a result of glutamate receptor activation in pathological conditions. I will also present data suggesting that NMDA receptors are not just a cause of damage to oligodendrocyte lineage cells, but that they can play a positive role in regulating myelination.

References 

Káradóttir, R, Hamilton, N., Bakiri, Y. & Attwell, D. 2008. Spiking and non-spiking classes of oligo-dendrocyte precursor glia in CNS white matter. Nature Neuroscience 11, 450–456.

Káradóttir, R., Cavelier, P., Bergersen L.H.& Attwell, D. 2005. NMDA receptors are expressed in oligodendrocytes and activated in ischaemia. Nature 438, 1162–1166.