The new findings, in a study funded by the National Institutes of Health, come from David Kornack, assistant professor of neurobiology and anatomy at the University of Rochester, and his former adviser, neuroscience pioneer Pasko Rakic of Yale.
“As a neuroscientist, oftentimes the first question I’m asked when I meet someone is, ‘How can I get more brain cells?’ I’m as interested in the question as everyone else,” says Kornack. “It’s now apparent that although some parts of the primate brain do acquire new neurons in adulthood, the neocortex is not among these regions.”
For decades, scientists believed that adult humans and other primates such as monkeys are born pretty much with all the nerve cells, or neurons, in the brain that they’ll ever have. However, in the last few years, several scientists equipped with new imaging techniques have reported growth of new neurons in adult primates like monkeys and humans in certain older parts of the brain, such as the hippocampus, which is key to memory, and the olfactory bulb, which is important for smell.
Two years ago, the idea took a giant step forward when researchers reported new neurons growing in the neocortex of adult monkeys. The neocortex – the wrinkled, outer layer of the brain – is the most evolved part of the brain, controlling our most sophisticated behaviors such as language and planning. The birth of new neurons in that part of the brain could have vast implications for human health and for understanding how the neocortex performs its sophisticated duties.
However, in the study published this week in Science, Rakic and Kornack used the most sophisticated cell analysis techniques available and found no new neurons in the neocortex of adult monkeys, despite painstaking analysis of thousands of new cells in the neocortex.
The team used two separate molecular markers to key in on candidates for new neurons, then used laser-based confocal microscopy to look closely at every candidate. They found that oftentimes a cell seemed to carry both signals, flagging it as a newly created neuron, but that when the team looked closely, the “new neuron” turned out to be two separate cells, usually one “old” neuron and one newly created cell of a different type, such as a glial cell.
The pair did find new neurons in the hippocampus and the olfactory bulb. And they did find new cells of other types, such as glial cells, in the neocortex. But the pair, who comprised one of the first teams of scientists to discover that new neurons can be made in the hippocampus of adult primates, did not detect a single new neuron in the neocortex, an idea which caused much excitement among neuroscientists two years ago.
One upshot of the new findings, Kornack says, is that scientists should look to mechanisms besides neurogenesis to understand the workings of the neocortex, such as how we learn and store memories over a lifetime. The work could also affect the development of therapies that use adult stem cells to replace neurons lost to brain injury or neurodegenerative diseases like Parkinson's or Alzheimer's.
“If we can find out what allows stem cells in those few restricted brain regions to continue producing neurons into adulthood, perhaps we can mimic that magic in other areas of the brain – such as the neocortex – that can suffer neuronal loss but don't normally make neurons," says Kornack, who left Yale to join the University of Rochester faculty last year. He is part of the University's Center for Aging and Developmental Biology.