Experiment Unveils Brain's Landscapers

Cold Spring Harbor Laboratory

Imagine yourself sometime in the far future aboard a routine rocket to Mars. Someone just spilled their drink. Without gravity, it collects in floating blobs that ripple right before your eyes. Now freeze.

What you see might look something like the above image from Cold Spring Harbor Laboratory's (CSHL's) Cheadle lab. But those purple and green blobs aren't the floating remains of somebody's drink. They're mysterious cells in the brain's visual cortex called OPCs.

The visual cortex processes everything we see. Incoming visual information is relayed to this outer layer of the brain via synapses—the silver streaks above. When the brain's neural circuits are first wired up, more connections, or synapses, are created than needed. As the brain accumulates new experiences and information, OPCs shape neural circuitry by pruning unnecessary synapses.

"OPCs are doing all sorts of things in the brain that help it to function in a normal, healthy way," CSHL Assistant Professor Lucas Cheadle says. OPCs are a specialty of the Cheadle lab. He and his team discovered OPCs' function as neural landscapers in 2022. Before that, they were thought only to produce oligodendrocytes, cells that sheath and support neurons. Now, Cheadle has developed new ways to zoom in and see OPCs in action.

"We're able to see what thousands of OPCs, and even smaller groups of 30-50, are doing," he explains. "From there, we can figure out which synapses are fully engulfed by an OPC, which are in the process of being pruned, and which have maybe just been checked on by an OPC but not processed."

The new techniques used to produce the image above have become essential tools in Cheadle's ongoing work. He and his team are now building on their 2022 discovery to help paint a complete picture of OPCs' role in health and disease. Cheadle explains: "These mysterious cells are one of the primary sources of glioma," a deadly brain cancer. "They're potentially involved in Alzheimer's disease as well."

It'll take more research to illustrate these connections in detail. In the meantime, Cheadle is eager to share his lab's new tools with researchers around the world. "The brain is constantly changing, and the same approaches you'd use to look at one type of cell can't just be applied across the board," he says. "We're adapting and innovating to keep up with it—to better understand how the brain works."

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