New cells are born every day in the brain's hippocampus, but what controls this birth has remained a mystery.
Reporting in the January 1 issue of Science , neuroscientists at the Johns Hopkins University School of Medicine have discovered that the birth of new cells, which depends on brain activity, also depends on a protein that is involved in changing epigenetic marks in the cell's genetic material.
"How is it that when you see someone you met ten years ago, you still recognize them? How do these transient events become long lasting in the brain, and what potential role does the birth of new neurons play in making these memories?" says Hongjun Song, Ph.D., an associate professor of neurology and member of the Johns Hopkins Institute of Cell Engineering's NeuroICE. "We really want to understand how daily life experiences trigger the birth and growth of new neurons, and make long-lasting changes in the brain."
The researchers reasoned that making long-term memories might require long-term changes in brain cells. And one type of cellular change that has long-lasting effects is so-called epigenetic change, which can alter a cell's DNA without changing its sequence but does change how and which genes are turned on or off. So they decided to look at the 40 to 50 genes known to be involved in epigenetics, and see if any of them are turned on in mouse brain cells that have been stimulated with electroconvulsive therapy—shock treatment. "It's long been known that ECT induces neurogenesis in rodents and humans, so we used it as our test case to find what is triggered downstream to cause new cells to grow," says Song.
One gene turned on in response to ECT was Gadd45b, a gene previously implicated in immune system function and misregulated in brain conditions like autism. To confirm Gadd45b is turned up in response to brain activity, the researchers also examined mice experiencing a different activity. Exposure to new surroundings, the team found, also turns on Gadd45b in brain cells.