Year 3

Sending neural impulses quickly down a long nerve fiber requires a specialized type of insulation called myelin, made by a cell called an oligodendrocyte that wraps itself around neuronal projections. Myelin-insulated nerve fibers make up the “white matter” of the brain, the vast tracts that connect one information-processing area of the brain to another. We have now shown that neuronal activity prompts oligodendrocyte precursor cell (OPC) proliferation and differentiation into myelin-forming oligodendrocytes. Neuronal activity also causes an increase in the thickness of the myelin sheaths within the active neural circuit, making signal transmission along the neural fiber more efficient. This was found to be true in both juvenile and in adult brains Metaphorically, it’s much like a system for improving traffic flow along roadways that are heavily used. And as with a transportation system, improving the routes that are most productive makes the whole system more efficient.
Interestingly, some parts of the neural circuit studied showed evidence of myelin-forming precursor cell response to neuronal activity, while other parts of the active circuit did not. In related and ongoing work, we are making progress towards understanding how OPCs differ in various regions of the brain, examining the molecular heterogeneity of human OPCs at a single cell level. We are also working hard to understand the molecular signals responsible for these “use-dependent” changes in white matter.
In a related follow-on project, we tested the idea that certain forms of brain cancer called “gliomas”, thought to be related to normal OPCs, may similarly respond to neuronal activity by proliferating and growing. Using a range of patient-derived glioma cell cultures, including glioblastoma, anaplastic oligodendroglioma and diffuse intrinsic pontine glioma (DIPG), we found that indeed high-grade glioma brain cancer cells grow more when exposed to molecules secreted in response to neuronal activity. In other words, the brain tumors are “hijacking” a mechanism of normal brain plasticity to promote the cancer growth. We went on to identify some of these neuronal-activity regulated factors glioma cells use for growth and we are now working to translate these findings into new therapies for this devastating type of brain cancer.