Through their pattern of firing, neurons influence the behavior of the cells that upon maturation will provide insulation of neuronal axons. A new study published yesterday in PLOS Biology by Balint Nagy, Maria Kukley, and colleagues at the University of Tübingen, Germany suggests the existence of a complex and nuanced interplay between neurons and the non-neuronal cells that support and protect them.
Previous work has shown that electrical or optical stimulation of nerve fibers influences the proliferation of oligodendrocyte precursor cells (OPCs) and their differentiation into oligodendrocytes, cells that insulate neuronal axons. However, whether that stimulation acts like an on-off switch, influencing OPCs only by its presence or absence, or more like a dimmer switch, inducing a graded response in the OPC, has been unclear.
The authors studied oligodendroglial cells in the corpus callosum, a nerve tract that connects the two hemispheres of the brain, both in fresh brain slices and in living rodents. Using electrodes, they stimulated neurons to fire and recorded responses in the neighboring OPCs.
They found that stimulating neuronal fibers in brain slices at low frequencies led to a slowly oscillating movement of ions through the membrane of OPCs, while high-frequency stimulation caused a much more rapidly oscillating movement of ions. While in living rodents, the high-frequency stimulation of neuronal fibers led to greater OPC proliferation and the lower-frequency stimulation led to more OPCs differentiating into pre-myelinating oligodendrocytes.
The differences in firing pattern have been seen to affect gene expression in more of a grader rather than an on-off switch. The neuronal firing patterns affect the properties of chemical synapses between neurons and OPC and intracellular concentrations of ions in OPCs. This shows that it may be possible that neurons use synapses with OPCs to influence OPCs behavior.
"This research may open new perspective to therapy of demyelinating disorders where remyelination strongly relies on the increased proliferation and differentiation of OPCs," commented Kukley.
Image: High-frequency stimulation is more efficient in promoting proliferation of Oligodendrocyte precursor cells (top row); low-frequency stimulation is more efficient in promoting differentiation of OPCs into pre-myelinating oligodendrocytes that are expected to further develop into oligodendrocytes and build myelin sheaths around the axon (bottom row). Image courtesy of Balint Nagy.