NG2 glial cells integrate synaptic input in global and dendritic calcium signals

Abstract

Synaptic signaling to NG2-expressing oligodendrocyte precursor cells (NG2 cells) could be key to rendering myelination of axons dependent on neuronal activity, but it has remained unclear whether NG2 glial cells integrate and respond to synaptic input. Here we show that NG2 cells perform linear integration of glutamatergic synaptic inputs and respond with increasing dendritic calcium elevations. Synaptic activity induces rapid Ca2+ signals mediated by low-voltage activated Ca2+ channels under strict inhibitory control of voltage-gated A-type K+ channels. Ca2+ signals can be global and originate throughout the cell. However, voltage-gated channels are also found in thin dendrites which act as compartmentalized processing units and generate local calcium transients. Taken together, the activity-dependent control of Ca2+ signals by A-type channels and the global versus local signaling domains make intracellular Ca2+ in NG2 cells a prime signaling molecule to transform neurotransmitter release into activity-dependent myelination.DOI: http://dx.doi.org/10.7554/eLife.16262.001

Oligodendroglia-lineage cells in brain plasticity, homeostasis and psychiatric disorders

“…Several studies have demonstrated that the close relationship of NG2-glia with the nodes of Ranvier is a cellular property of these cells to monitor the axonal myelination upon neuronal activity [46–48]. NG2-glia’s complex, stellate branches closely associate with neuronal soma and dendrites [39,49,50].…”

“…NG2-glia’s complex, stellate branches closely associate with neuronal soma and dendrites [39,49,50]. Recent work has shown NG2-glia to be specialized integrators of incoming synaptic activity from individual axons encoding the number of active synapses in a graded fashion towards different functional outcomes [48]. The synaptic transmission machinery of unidirectional neuron-to-NG2 glia synapse is remarkably similar to that of the traditional synapse.…”

NG2 Glia: Novel Roles beyond Re-/Myelination

“…Of note, NG2 glia have been reported to detect fine changes of extracellular potassium concentration due to the discharge of a single neuron via the inward-rectifier Kir4.1 potassium channels [78,80]. Similarly, by employing two-photon-based glutamate uncaging to produce very localized and brief release of glutamate onto NG2 glia processes segments, Sun et al [81] showed that small neurotransmitter release events at neuron-to-NG2 cell synapses can be sensed via the generation of local depolarizations and, consequentially, local Ca 2+ signals in NG2 glia processes.…”

“…The incoming electrical synaptic inputs are temporally and spatially summed and integrated by NG2 glia, by using Ca 2+ levels to proportionally encode the number of the active synapses [81]. Interestingly, by analysing the properties of ionic currents elicited by repetitive axonal stimulation at glutamatergic neuron-to-NG2 glia synapses, Nagy et al [77] recently demonstrated that, similar to neurons, NG2 glia are also able to discriminate different patterns of presynaptic axonal activity (i.e., stimulation trains with distinct frequency of pulses).…”

Rebound from Inhibition: Self-Correction against Neurodegeneration?

“…Examination of this feature of PSCs in the G37R mutant SOD1 transgenic ALS mouse model suggests that PSCs abnormally decode hyperexcitability at the neuromuscular junction, fail to transition into their reparative state, and thus contribute to NMJ denervation [76]. Since NG2 cells also integrate global and dendritic calcium signals and display calcium transients in response to neural activity [77], it suggests that similar mechanisms may be operating at rebound neuron synapses during rhythmic circuit disruption. Interestingly, deletion of NG2 cells in the CNS has no obvious neuropathologic sequelae per se [78], however, a detailed examination of associated neuronal activities has yet to be examined under conditions where they have been knocked out globally, so it may be premature to speculate on whether their presence is critical for normal circuit function.…”