For normal function of the nervous system, oligodendrocytes are needed to speed the propagation of the action potential. In diseases like cerebral palsy, spinal cord injury and multiple sclerosis, oligodendrocytes get damaged and the action potential is slowed or abolished. Replacement of damaged oligodendrocytes, either by endogenous or perhaps transplanted cells, is essential to restore normal function. In the adult brain more than 5% of the cells are glia that express the proteoglycan NG2 (Dawson et al. 2003). The function of these cells is poorly understood. They are generally thought to be oligodendrocyte precursor cells, which might replace myelinating oligodendrocytes that become damaged. However, they have recently been suggested to be either multipotent stem cells able to generate both GABAergic neurons and oligodendrocytes (Aguirre et al. 2004), or a new type of glia called synantocytes which contact the nodes of Ranvier (Butt et al. 1999). Because of this controversy over their function, we have examined the origins of these cells with immunohistochemistry and studied their electrical properties by whole-cell clamping. Dye filling from the whole-cell pipette allowed us to study the cells’ morphology and recover the recorded cell for antibody labelling (Káradóttir et al. 2005). In the white matter of cerebellar slices at postnatal day 7, most NG2 glia are part of the oligodendrocyte lineage: 93% of 106 cells which labelled with antibody to NG2 were also labelled by antibody against the oligodendrocyte transcription factor Olig2. However, these NG2/Olig2 positive cells could be divided into two subtypes with distinct electrophysiological properties. One subtype showed a TTX-sensitive sodium current, followed by a slowly developing outward rectifying current presumably mediated by voltage-gated potassium channels, in response to depolarizing voltage steps. The other subtype did not show these voltage-gated currents. Interestingly, although both subtypes responded to superfused GABA and glutamate, only the subtype expressing the voltage-gated channels also received action potential driven synaptic input, both GABA-ergic and glutamatergic, which was TTX sensitive. These data suggest that two subtypes of oligodendrocyte precursor exist, with distinct electrophysiological characteristics, contrary to current assumptions. Only the subtype expressing voltage-gated channels senses its neuronal environment by receiving synaptic input from passing axons. Conceivably one of these subtypes may be destined to myelinate axons immediately, and the other may become the ‘adult precursors’ which can differentiate into myelinating oligodendrocytes after pathological conditions.
University College London 2006 (2006) Proc Physiol Soc 3, PC163
Poster Communications: Different subtypes of NG2-positive glia in the white matter of rat cerebellar slices
Ragnhildur Thora Karadottir1, David Attwell1
1. Department of Physiology, University College London, London, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.