Neurotransmitter-mediated damage to oligodendrocytes contributes to mental or physical handicap in periventricular leukomalacia leading to cerebral palsy, spinal cord injury, multiple sclerosis and stroke. In cerebellar slices, we found that whole-cell clamped oligodendrocytes respond to glutamate or GABA by generating an inward current. The GABA response was generated by GABAA receptors, with the Cl- reversal potential positive to the resting potential (~ -60mV). Until recently it was believed that, unlike neurons, oligodendrocytes lack NMDA receptors and that glutamate generates a current in oligodendrocytes by acting on AMPA/kainate receptors. We found, however, that oligodendrocytes also exhibit NMDA-evoked currents at all developmental stages, mediated by receptors which show a much weaker Mg2+ -block than neuronal NMDA receptors, and may contain NR1, NR2C and NR3 subunits (Káradóttir et al., 2005). Simulating ischaemia led to an inward current developing in oligodendrocytes. This was mediated partly by NMDA and AMPA/KA receptors, and partly by GABAA receptors. Thus, ischaemia evokes a release of both glutamate and GABA in the white matter, both of which transmitters depolarize oligodendrocytes. These data point to NMDA receptors of unusual subunit composition as a novel therapeutic target for preventing white matter damage in a range of diseases.

Supported by the Wellcome Trust & Norwegian Research Council

REFERENCE

Káradóttir, R., Cavelier, P., Bergersen, L. & Attwell, D. 2005. Nature 438, 1162-1166.