Electrical signalling properties of oligodendrocyte precursor cells

Abstract

yamina bakiri 1 , david attwell 1 and ragnhildur kara ' do ' ttir 2Oligodendrocyte precursor cells (OPCs) have become the focus of intense research, not only because they generate myelinforming oligodendrocytes in the normal CNS, but because they may be suitable for transplantation to treat disorders in which myelin does not form or is damaged, and because they have stem-cell-like properties in that they can generate astrocytes and neurons as well as oligodendrocytes. In this article we review the electrical signalling properties of OPCs, including the synaptic inputs they receive and their use of voltage-gated channels to generate action potentials, and we describe experiments attempting to detect output signalling from OPCs. We discuss controversy over the existence of different classes of OPC with different electrical signalling properties, and speculate on the lineage relationship and myelination potential of these different classes of OPC. Finally, we point out that, since OPCs are the main proliferating cell type in the mature brain, the discovery that they can develop into neurons raises the question of whether more neurons are generated in the mature brain from the classical sites of neurogenesis in the subventricular zone of the lateral ventricle and the hippocampal dentate gyrus or from the far more widely distributed OPCs.Keywords: Myelin, OPC, NG2, stem cell, neuron I N T R O D U C T I O NOligodendrocyte precursor cells (OPCs) transform into myelinating oligodendrocytes during development (Nishiyama et al., 2002), but are also present in the adult CNS where they comprise 5% of the cells and are the main proliferating cell type (Horner et al., 2000;Stallcup, 2002; Dawson et al., 2003). Damage to oligodendrocyte precursors, leading to reduced myelination, contributes to mental and physical impairment in periventricular leukomalacia (pre-or perinatal white matter injury leading to cerebral palsy; Volpe, 2001). Adult OPCs may form new myelinating oligodendrocytes in multiple sclerosis, and in brain or spinal cord injury (Levine, 1994;Gensert and Goldman, 1997;Keirstead et al., 1998;McTigue et al., 2001;Levine et al., 2001;Horner et al., 2002), and OPC transplants could serve as a basis for therapeutic remyelination (Windrem et al., 2008;Moreno-Manzano et al., 2009). This article will focus on the electrical signalling properties of OPCs which, as we will describe below, may play a crucial role in their development and their myelination of axons. D E F I N I N G O P C sIn the next section we will review several papers suggesting that OPCs are not a homogenous set of cells, but fall into at least two classes. To establish the range of properties of OPCs, it is essential to have criteria to define which cells are OPCs; so we will preface our review by examining the techniques available for doing this, and their advantages and pitfalls.Classically, OPCs have been defined antigenically, both in culture and in situ, by their expression of the proteoglycan NG2 (Nishiyama et al., 1996), the growth factor recept...

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