Abstract
Oligodendrocyte precursor cells (OPCs) originate in localized germinal zones in the embryonic neural tube, then migrate and proliferate to populate the entire central nervous system, both white and gray matter. They divide and generate myelinating oligodendrocytes (OLs) throughout postnatal and adult life. OPCs express NG2 and platelet-derived growth factor receptor alpha subunit (PDGFRα), two functionally important cell surface proteins, which are also widely used as markers for OPCs. The proliferation of OPCs, their terminal differentiation into OLs, survival of new OLs, and myelin synthesis are orchestrated by signals in the local microenvironment. We discuss advances in our mechanistic understanding of paracrine effects, including those mediated through PDGFRα and neuronal activity-dependent signals such as those mediated through AMPA receptors in OL survival and myelination. Finally, we review recent studies supporting the role of new OL production and “adaptive myelination” in specific behaviours and cognitive processes contributing to learning and long-term memory formation. Our article is not intended to be comprehensive but reflects the authors’ past and present interests.
Highlights
Oligodendrocyte precursor cells (OPCs) originate in localized germinal zones in the embryonic neural tube, migrate and proliferate to populate the entire central nervous system, both white and gray matter
Myelinating cells arise from committed oligodendrocyte (OL) pre cursor cells (OPCs) that appear in discrete regions of the ventral ven tricular zones (VZ) of the brain and spinal cord during mid- to late gestation, and subsequently in the dorsal VZ
What are the activity-related myelin-promoting signals? Glutamate is a prime suspect because OPCs and/or OLs express all of the wellknown ionotropic glutamate receptor families – AMPA-type receptors (AMPAR), kainate receptors (KAR) and NMDA receptors (NMDAR) – in addition to metabotropic receptors
Summary
Myelinating cells arise from committed oligodendrocyte (OL) pre cursor cells (OPCs) that appear in discrete regions of the ventral ven tricular zones (VZ) of the brain and spinal cord during mid- to late gestation, and subsequently in the dorsal VZ (reviewed in references [1, 2]). During the postnatal period of rapid OL production that precedes and accom panies myelination, many of the recently divided OPCs give rise to two differentiated OLs, whereas in the mature central nervous system (CNS) most OPC divisions are self-renewing, generating either one OL and a replacement OPC, or two OPCs [3,4]. This leads to an age-dependent decline in the rate of OL production (Fig. 1). There certainly are exceptions and some known species-specific differences, which can be informative in their own right, are discussed below
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