Excitability and Synaptic Communication within the Oligodendrocyte Lineage

Abstract

The mammalian CNS contains an abundant, widely distributed population of glial cells that serve as oligodendrocyte progenitors. It has been reported that these NG2-immunoreactive cells (NG2 ϩ cells) form synapses and generate action potentials, suggesting that neuralevoked excitation of these progenitors may regulate oligodendrogenesis. However, recent studies also suggest that NG2 ϩ cells are comprised of functionally distinct groups that differ in their ability to respond to neuronal activity, undergo differentiation, and experience injury following ischemia. To better define the physiological properties of NG2 ϩ cells, we used transgenic mice that allowed an unbiased sampling of this population and unambiguous identification of cells in discrete states of differentiation. Using acute brain slices prepared from developing and mature mice, we found that NG2 ϩ cells in diverse brain regions share a core set of physiological properties, including expression of voltage-gated Na ϩ (NaV) channels and ionotropic glutamate receptors, and formation of synapses with glutamatergic neurons. Although small amplitude Na ϩ spikes could be elicited in some NG2 ϩ cells during the first postnatal week, they were not capable of generating action potentials. Transition of these progenitors to the premyelinating stage was accompanied by the rapid removal of synaptic input, as well as downregulation of AMPA and NMDA receptors and NaV channels. Thus, prior reports of physiological heterogeneity among NG2 ϩ cells may reflect analysis of cells in later stages of maturation. These results suggest that NG2 ϩ cells are uniquely positioned within the oligodendrocyte lineage to monitor the firing patterns of surrounding neurons.

Ecotropic Murine Leukemia Virus Infection of Glial Progenitors Interferes with Oligodendrocyte Differentiation: Implications for Neurovirulence

“…The presence of excitatory neurotransmitter receptors on these cells makes them particularly susceptible to glutamate-mediated damage (41,70). With the developmental maturation of OPCs to OLs, cells downregulate expression of the calcium-permeable ionotropic receptors, reducing their susceptibility to excitotoxic insult (71). Given our recent report demonstrating that FrCasE glial infection in the inferior colliculus causes rebound neuron hyperexcitability, coincident infection of NG2 glia would be expected to suspend those cells in the OPC state, rendering them persistently susceptible to excitoxic challenge.…”

Oligodendrocyte Development and Plasticity

“…They are also transient within the lineage. AMPA and NMDA receptor expression is rapidly down-regulated and synapses are removed when OPCs begin to differentiate, indicating that the precursor stage is uniquely specialized to engage in rapid communication with neurons (De Biase et al 2010;Kukley et al 2010). In neurons, excitatory synapses induce depolarization to allow Ca 2þ influx through NMDA receptors and voltage-gated Ca 2þ channels, and initiate action potentials to induce changes in synaptic strength, gene expression, and to enable rapid transfer of information.…”

Dynamic Modulation of Myelination in Response to Visual Stimuli Alters Optic Nerve Conduction Velocity

“…Oligodendroglial cells express a wide repertoire of neurotransmitter receptors, including ionotropic and metabotropic glutamate receptors. In all brain regions examined, neurons and OPCs communicate via classic chemical glutamatergic synapses that elicit AMPAR-mediated postsynaptic currents in OPCs (Kukley et al, 2007;Ziskin et al, 2007;De Biase et al, 2010). This axon-OPC signaling is uniquely positioned to monitor the firing patterns of surrounding neurons and mediate activity-and experience-dependent fine-tuning of myelination.…”